diff --git a/README.md b/README.md
index 5b6739338e..1d9138c167 100644
--- a/README.md
+++ b/README.md
@@ -41,6 +41,9 @@ This is the JavaScript version of [OpenTelemetry](https://opentelemetry.io/), a
 
 ## Quick Start
 
+**Much of OpenTelemetry JS documentation is written assuming the compiled application is run as CommonJS.**
+For more details on ECMAScript Modules vs CommonJS, refer to [esm-support](https://github.com/open-telemetry/opentelemetry-js/blob/main/doc/esm-support.md).
+
 The following describes how to set up tracing for a basic web application.
 For more detailed documentation, see the website at <https://opentelemetry.io/docs/instrumentation/js/>.
 
@@ -110,7 +113,7 @@ If you are a library author looking to build OpenTelemetry into your library, pl
 ## Supported Runtimes
 
 | Platform Version    | Supported                                     |
-|---------------------|-----------------------------------------------|
+| ------------------- | --------------------------------------------- |
 | Node.JS `v22`       | :heavy_check_mark:                            |
 | Node.JS `v20`       | :heavy_check_mark:                            |
 | Node.JS `v18`       | :heavy_check_mark:                            |
@@ -143,13 +146,13 @@ There may also be API packages for experimental signals in the experimental dire
 All stable packages are released with the same version, and all experimental packages are released with the same version.
 The below table describes which versions of each set of packages are expected to work together.
 
-| Stable Packages                                                 | Experimental Packages |
-|-----------------------------------------------------------------|-----------------------|
-| 1.21.x                                                          | 0.48.x                |
-| 1.20.x                                                          | 0.47.x                |
-| 1.19.x                                                          | 0.46.x                |
-| 1.18.x                                                          | 0.45.x                |
-| 1.17.x                                                          | 0.44.x                |
+| Stable Packages | Experimental Packages |
+| --------------- | --------------------- |
+| 1.21.x          | 0.48.x                |
+| 1.20.x          | 0.47.x                |
+| 1.19.x          | 0.46.x                |
+| 1.18.x          | 0.45.x                |
+| 1.17.x          | 0.44.x                |
 
 <details>
 <summary>Older version compatibility matrix</summary>
diff --git a/doc/esm-support.md b/doc/esm-support.md
new file mode 100644
index 0000000000..e9abc70aa2
--- /dev/null
+++ b/doc/esm-support.md
@@ -0,0 +1,131 @@
+# ECMAScript Modules vs. CommonJS
+
+Node.js uses a different module loader for ECMAScript Modules (ESM) vs. CommonJS (CJS).
+To verify whether your application is ESM or CJS, refer to [Node.js docs for Determining Module System](https://nodejs.org/api/packages.html#determining-module-system).
+
+An `.mjs` extension or `type:module` in the built app's `package.json` indicates the app is ESM.
+
+**Much of OpenTelemetry JS documentation is written assuming the compiled application is run as CJS.**
+ESM support is ongoing; a few adjustments are needed for configuration and startup commands.
+
+For more explanation about CJS and ESM, see the [Node.js docs](https://nodejs.org/api/modules.html#enabling).
+
+## TypeScript
+
+Many TypeScript projects today are written using ESM syntax, regardless of how they are compiled.
+In the `tsconfig.json`, there is an option to compile to ESM or CJS.
+If the compiled code is ESM, those import statements will remain the same (e.g. `import { foo } from 'bar';`).
+If the compiled code is CJS, those import statements will become `require()` statements (e.g. `const { foo } = require('bar');`)
+
+## Initializing the SDK
+
+Instrumentation setup and configuration must be run before your application code.
+If the SDK is initialized in a separate file (recommended), ensure it is imported first in application startup, or use the `--require` or `--import` flag during startup to preload the module.
+
+For CJS, the `NODE_OPTIONS` for the startup command should include `--require ./telemetry.js`.
+
+For ESM, minimum Node.js version of `18.19.0` is required.
+The `NODE_OPTIONS` for the startup command should include `--import ./telemetry.js`.
+
+## Instrumentation Hook Required for ESM
+
+If your application is written in JavaScript as ESM, or compiled to ESM from TypeScript, then a loader hook is required to properly patch instrumentation.
+The custom hook for ESM instrumentation is `--experimental-loader=@opentelemetry/instrumentation/hook.mjs`.
+This flag must be passed to the `node` binary, which is often done as a startup command and/or in the `NODE_OPTIONS` environment variable.
+
+### Additional Notes on Experimental Loaders
+
+Though the OpenTelemetry loader currently relies on `import-in-the-middle`, direct usage of `import-in-the-middle/hook.mjs` may cease to work in the future.
+The only currently supported loader hook is `@opentelemetry/instrumentation/hook.mjs`.
+
+**Note:** Eventually the recommendation for how to setup OpenTelemetry for usage with ESM will change to no longer require `--experimental-loader=@opentelemetry/instrumentation/hook.mjs`.
+Instead the bootstrap code (in `./telemetry.js`) will use Node.js's newer `module.register(...)`.
+Refer to this [issue](https://github.com/open-telemetry/opentelemetry-js/issues/4933) for details.
+
+Because of ongoing issues with loaders running TypeScript code as ESM in development environments, results may vary.
+
+To use `ts-node` to run the uncompiled TypeScript code, the module must be CJS.
+To use `tsx` to run the uncompiled TypeScript code as ESM, the `--import` flag must be used.
+
+## Using the Zero Code Option with `auto-instrumentations-node`
+
+The `auto-instrumentations-node` package contains a `register` entry-point that can be used with `--require` or `--import` to setup and start the SDK easily, without application code changes.
+For ESM, the package also requires the usage of the loader hook.
+
+Startup command for CJS:
+
+```sh
+node --require @opentelemetry/auto-instrumentations-node/register app.js
+```
+
+Startup command for ESM:
+
+```sh
+node --experimental-loader=@opentelemetry/instrumentation/hook.mjs --import @opentelemetry/auto-instrumentations-node/register app.js
+```
+
+## Examples
+
+### Example Written in JavaScript as CJS
+
+```javascript
+/*telemetry.cjs*/
+const { NodeSDK } = require('@opentelemetry/sdk-node');
+const { ConsoleSpanExporter } = require('@opentelemetry/sdk-trace-node');
+const {
+  getNodeAutoInstrumentations,
+} = require('@opentelemetry/auto-instrumentations-node');
+
+const sdk = new NodeSDK({
+  traceExporter: new ConsoleSpanExporter(),
+  instrumentations: [getNodeAutoInstrumentations()],
+});
+
+sdk.start();
+```
+
+Startup command:
+
+```sh
+node --require ./telemetry.cjs app.js
+```
+
+### Example Written in JavaScript as ESM or TypeScript
+
+```typescript
+/*telemetry.ts | telemetry.mjs*/
+import { NodeSDK } from '@opentelemetry/sdk-node';
+import { ConsoleSpanExporter } from '@opentelemetry/sdk-trace-node';
+import { getNodeAutoInstrumentations } from '@opentelemetry/auto-instrumentations-node';
+
+const sdk = new NodeSDK({
+  traceExporter: new ConsoleSpanExporter(),
+  instrumentations: [getNodeAutoInstrumentations()],
+});
+
+sdk.start();
+```
+
+Startup command for compiled CJS:
+
+```sh
+node --require ./telemetry.js app.js
+```
+
+Startup command for compiled ESM:
+
+```sh
+node --experimental-loader=@opentelemetry/instrumentation/hook.mjs --import ./telemetry.js app.js
+```
+
+### ESM Options for Different Versions of Node.js
+
+The entire startup command should include the following `NODE_OPTIONS`:
+
+| Node.js Version   | NODE_OPTIONS                                                                              |
+| ----------------- | ----------------------------------------------------------------------------------------- |
+| 16.x              | `--require ./telemetry.cjs --experimental-loader=@opentelemetry/instrumentation/hook.mjs` |
+| >=18.1.0 <18.19.0 | `--require ./telemetry.cjs --experimental-loader=@opentelemetry/instrumentation/hook.mjs` |
+| ^18.19.0          | `--import ./telemetry.mjs --experimental-loader=@opentelemetry/instrumentation/hook.mjs`  |
+| 20.x              | `--import ./telemetry.mjs --experimental-loader=@opentelemetry/instrumentation/hook.mjs`  |
+| 22.x              | `--import ./telemetry.mjs --experimental-loader=@opentelemetry/instrumentation/hook.mjs`  |
diff --git a/experimental/packages/opentelemetry-instrumentation/README.md b/experimental/packages/opentelemetry-instrumentation/README.md
index 3e422a59d6..865592e282 100644
--- a/experimental/packages/opentelemetry-instrumentation/README.md
+++ b/experimental/packages/opentelemetry-instrumentation/README.md
@@ -7,6 +7,9 @@
 
 ## Installation
 
+**Note: Much of OpenTelemetry JS documentation is written assuming the compiled application is run as CommonJS.**
+For more details on ECMAScript Modules vs CommonJS, refer to [esm-support](https://github.com/open-telemetry/opentelemetry-js/blob/main/doc/esm-support.md).
+
 ```bash
 npm install --save @opentelemetry/instrumentation
 ```
@@ -108,7 +111,7 @@ export class MyInstrumentation extends InstrumentationBase {
 
 // Later, but before the module to instrument is required
 
-const myInstrumentationn = new MyInstrumentation();
+const myInstrumentation = new MyInstrumentation();
 myInstrumentation.setTracerProvider(provider); // this is optional, only if global TracerProvider shouldn't be used
 myInstrumentation.setMeterProvider(meterProvider); // this is optional
 myInstrumentation.enable();
@@ -219,12 +222,17 @@ If nothing is specified the global registered provider is used. Usually this is
 There might be use case where someone has the need for more providers within an application. Please note that special care must be takes in such setups
 to avoid leaking information from one provider to the other because there are a lot places where e.g. the global `ContextManager` or `Propagator` is used.
 
-## Instrumentation for ES Modules In Node.js (experimental)
+## Instrumentation for ECMAScript Modules (ESM) in Node.js (experimental)
+
+Node.js uses a different module loader for ECMAScript Modules (ESM) vs. CommonJS (CJS).
+A `require()` call will cause Node.js to use the CommonJS module loader.
+An `import ...` statement or `import()` call will cause Node.js to use the ECMAScript module loader.
 
-As the module loading mechanism for ESM is different than CJS, you need to select a custom loader so instrumentation can load hook on the ESM module it want to patch. To do so, you must provide the `--experimental-loader=@opentelemetry/instrumentation/hook.mjs` flag to the `node` binary. Alternatively you can set the `NODE_OPTIONS` environment variable to `NODE_OPTIONS="--experimental-loader=@opentelemetry/instrumentation/hook.mjs"`.
-As the ESM module loader from Node.js is experimental, so is our support for it. Feel free to provide feedback or report issues about it.
+If your application is written in JavaScript as ESM, or it must compile to ESM from TypeScript, then a loader hook is required to properly patch instrumentation.
+The custom hook for ESM instrumentation is `--experimental-loader=@opentelemetry/instrumentation/hook.mjs`.
+This flag must be passed to the `node` binary, which is often done as a startup command and/or in the `NODE_OPTIONS` environment variable.
 
-**Note**: ESM Instrumentation is not yet supported for Node 20.
+For more details on ECMAScript Modules vs CommonJS, refer to [esm-support](https://github.com/open-telemetry/opentelemetry-js/blob/main/doc/esm-support.md).
 
 ## Limitations
 
diff --git a/experimental/packages/opentelemetry-sdk-node/README.md b/experimental/packages/opentelemetry-sdk-node/README.md
index e2e5fe39d6..4d0ffd0b50 100644
--- a/experimental/packages/opentelemetry-sdk-node/README.md
+++ b/experimental/packages/opentelemetry-sdk-node/README.md
@@ -9,6 +9,9 @@ This package provides the full OpenTelemetry SDK for Node.js including tracing a
 
 ## Quick Start
 
+**Note: Much of OpenTelemetry JS documentation is written assuming the compiled application is run as CommonJS.**
+For more details on ECMAScript Modules vs CommonJS, refer to [esm-support](https://github.com/open-telemetry/opentelemetry-js/blob/main/doc/esm-support.md).
+
 To get started you need to install `@opentelemetry/sdk-node`, a metrics and/or tracing exporter, and any appropriate instrumentation for the node modules used by your application.
 
 ### Installation
@@ -191,19 +194,19 @@ This is an alternative to programmatically configuring an exporter or span proce
 
 ### Exporters
 
-| Environment variable | Description |
-|----------------------|-------------|
+| Environment variable | Description                                                                                                                                                                        |
+| -------------------- | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
 | OTEL_TRACES_EXPORTER | List of exporters to be used for tracing, separated by commas. Options include `otlp`, `jaeger`, `zipkin`, and `none`. Default is `otlp`. `none` means no autoconfigured exporter. |
-| OTEL_LOGS_EXPORTER | List of exporters to be used for logging, separated by commas. Options include `otlp`, `console` and `none`. Default is `otlp`. `none` means no autoconfigured exporter. |
+| OTEL_LOGS_EXPORTER   | List of exporters to be used for logging, separated by commas. Options include `otlp`, `console` and `none`. Default is `otlp`. `none` means no autoconfigured exporter.           |
 
 ### OTLP Exporter
 
-| Environment variable | Description |
-|----------------------|-------------|
-| OTEL_EXPORTER_OTLP_PROTOCOL | The transport protocol to use on OTLP trace, metric, and log requests. Options include `grpc`, `http/protobuf`, and `http/json`. Default is `http/protobuf`. |
-| OTEL_EXPORTER_OTLP_TRACES_PROTOCOL | The transport protocol to use on OTLP trace requests. Options include `grpc`, `http/protobuf`, and `http/json`. Default is `http/protobuf`. |
-| OTEL_EXPORTER_OTLP_METRICS_PROTOCOL | The transport protocol to use on OTLP metric requests. Options include `grpc`, `http/protobuf`, and `http/json`. Default is `http/protobuf`. |
-| OTEL_EXPORTER_OTLP_LOGS_PROTOCOL | The transport protocol to use on OTLP log requests. Options include `grpc`, `http/protobuf`, and `http/json`. Default is `http/protobuf`. |
+| Environment variable                | Description                                                                                                                                                  |
+| ----------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------ |
+| OTEL_EXPORTER_OTLP_PROTOCOL         | The transport protocol to use on OTLP trace, metric, and log requests. Options include `grpc`, `http/protobuf`, and `http/json`. Default is `http/protobuf`. |
+| OTEL_EXPORTER_OTLP_TRACES_PROTOCOL  | The transport protocol to use on OTLP trace requests. Options include `grpc`, `http/protobuf`, and `http/json`. Default is `http/protobuf`.                  |
+| OTEL_EXPORTER_OTLP_METRICS_PROTOCOL | The transport protocol to use on OTLP metric requests. Options include `grpc`, `http/protobuf`, and `http/json`. Default is `http/protobuf`.                 |
+| OTEL_EXPORTER_OTLP_LOGS_PROTOCOL    | The transport protocol to use on OTLP log requests. Options include `grpc`, `http/protobuf`, and `http/json`. Default is `http/protobuf`.                    |
 
 Additionally, you can specify other applicable environment variables that apply to each exporter such as the following:
 
diff --git a/packages/opentelemetry-sdk-trace-node/README.md b/packages/opentelemetry-sdk-trace-node/README.md
index 28c5d9fa72..aebf29a017 100644
--- a/packages/opentelemetry-sdk-trace-node/README.md
+++ b/packages/opentelemetry-sdk-trace-node/README.md
@@ -8,6 +8,9 @@ This module provides *automated instrumentation and tracing* for Node.js applica
 For manual instrumentation see the
 [@opentelemetry/sdk-trace-base](https://github.com/open-telemetry/opentelemetry-js/tree/main/packages/opentelemetry-sdk-trace-base) package.
 
+**Note: Much of OpenTelemetry JS documentation is written assuming the compiled application is run as CommonJS.**
+For more details on ECMAScript Modules vs CommonJS, refer to [esm-support](https://github.com/open-telemetry/opentelemetry-js/blob/main/doc/esm-support.md).
+
 ## How auto instrumentation works
 
 This package exposes a `NodeTracerProvider`.