diff --git a/.github/workflows/test.yml b/.github/workflows/test.yml
index c8e3209..c55a025 100644
--- a/.github/workflows/test.yml
+++ b/.github/workflows/test.yml
@@ -20,3 +20,12 @@ jobs:
         node-version: ${{ matrix.node }}
     - run: npm install
     - run: npm test
+    # Run the webpack tests for Node.js versions that webpack[-cli] support.
+    - run: npm run test:webpack
+      if: ${{ matrix.node != '8.10'
+        && matrix.node != '10.0'
+        && matrix.node != '10'
+        && matrix.node != '12.0'
+        && matrix.node != '12'
+        && matrix.node != '14.0'
+        && matrix.node != '14' }}
diff --git a/.gitignore b/.gitignore
index ffff996..16e5df5 100644
--- a/.gitignore
+++ b/.gitignore
@@ -3,3 +3,4 @@
 /tmp
 /require-in-the-middle-*.tgz
 *.example.js
+test/webpack/dist/
diff --git a/index.js b/index.js
index d3d49f9..13c3e19 100644
--- a/index.js
+++ b/index.js
@@ -5,6 +5,14 @@ const Module = require('module')
 const debug = require('debug')('require-in-the-middle')
 const moduleDetailsFromPath = require('module-details-from-path')
 
+// Webpack replaces `require` with its own fn that is insufficient for how
+// require is used in this package. It is strongly hoped no other
+// bundler-specific hacks are needed.
+/* global __non_webpack_require__ */
+const nativeRequire = typeof __webpack_require__ === 'function' // eslint-disable-line camelcase
+  ? __non_webpack_require__ // eslint-disable-line camelcase
+  : require
+
 // Using the default export is discouraged, but kept for backward compatibility.
 // Use this instead:
 //    const { Hook } = require('require-in-the-middle')
@@ -64,7 +72,7 @@ class ExportsCache {
     if (this._localCache.has(filename)) {
       return true
     } else if (!isBuiltin) {
-      const mod = require.cache[filename]
+      const mod = nativeRequire.cache[filename]
       return !!(mod && this._kRitmExports in mod)
     } else {
       return false
@@ -76,7 +84,7 @@ class ExportsCache {
     if (cachedExports !== undefined) {
       return cachedExports
     } else if (!isBuiltin) {
-      const mod = require.cache[filename]
+      const mod = nativeRequire.cache[filename]
       return (mod && mod[this._kRitmExports])
     }
   }
@@ -84,8 +92,8 @@ class ExportsCache {
   set (filename, exports, isBuiltin) {
     if (isBuiltin) {
       this._localCache.set(filename, exports)
-    } else if (filename in require.cache) {
-      require.cache[filename][this._kRitmExports] = exports
+    } else if (filename in nativeRequire.cache) {
+      nativeRequire.cache[filename][this._kRitmExports] = exports
     } else {
       debug('non-core module is unexpectedly not in require.cache: "%s"', filename)
       this._localCache.set(filename, exports)
@@ -273,7 +281,7 @@ function Hook (modules, options, onrequire) {
         // figure out if this is the main module file, or a file inside the module
         let res
         try {
-          res = require.resolve(moduleName, { paths: [basedir] })
+          res = nativeRequire.resolve(moduleName, { paths: [basedir] })
         } catch (e) {
           debug('could not resolve module: %s', moduleName)
           self._cache.set(filename, exports, core)
diff --git a/package.json b/package.json
index fe7cf14..c0569a9 100644
--- a/package.json
+++ b/package.json
@@ -18,13 +18,16 @@
     "roundround": "^0.2.0",
     "semver": "^6.3.0",
     "standard": "^14.3.1",
-    "tape": "^4.11.0"
+    "tape": "^4.11.0",
+    "webpack": "^5.105.0",
+    "webpack-cli": "^5.1.0"
   },
   "scripts": {
     "test": "npm run test:lint && npm run test:tape && npm run test:babel",
     "test:lint": "standard",
     "test:tape": "tape test/*.js",
-    "test:babel": "node test/babel/babel-register.js"
+    "test:babel": "node test/babel/babel-register.js",
+    "test:webpack": "webpack --config test/webpack/webpack.config.js && node test/webpack/dist/bundle.js # requires node 16+"
   },
   "repository": {
     "type": "git",
diff --git a/test/webpack/test.js b/test/webpack/test.js
new file mode 100644
index 0000000..7899250
--- /dev/null
+++ b/test/webpack/test.js
@@ -0,0 +1,22 @@
+'use strict'
+
+const assert = require('assert')
+
+const { Hook } = require('../../')
+
+const hooked = []
+
+// Hook all modules as @opentelemetry/instrumentation does.
+const hook = new Hook('*', function (exports, name, basedir) {
+  if (name === 'semver') {
+    hooked.push(name)
+    exports.patched = true
+  }
+  return exports
+})
+
+const semver = require('semver')
+assert.strictEqual(semver.patched, true)
+assert.deepStrictEqual(hooked, ['semver'])
+
+hook.unhook()
diff --git a/test/webpack/webpack.config.js b/test/webpack/webpack.config.js
new file mode 100644
index 0000000..7c67eed
--- /dev/null
+++ b/test/webpack/webpack.config.js
@@ -0,0 +1,16 @@
+'use strict'
+
+const path = require('path')
+
+module.exports = {
+  target: 'node',
+  mode: 'production',
+  entry: path.join(__dirname, 'test.js'),
+  output: {
+    path: path.join(__dirname, 'dist'),
+    filename: 'bundle.js'
+  },
+  externals: {
+    semver: 'commonjs semver'
+  }
+}