diff --git a/synapse/handlers/appservice.py b/synapse/handlers/appservice.py
index 0aba6238a5..b189eb95d0 100644
--- a/synapse/handlers/appservice.py
+++ b/synapse/handlers/appservice.py
@@ -33,7 +33,7 @@ from synapse.metrics.background_process_metrics import (
     wrap_as_background_process,
 )
 from synapse.storage.databases.main.directory import RoomAliasMapping
-from synapse.types import JsonDict, RoomAlias, RoomStreamToken, UserID
+from synapse.types import DeviceLists, JsonDict, RoomAlias, RoomStreamToken, UserID
 from synapse.util.async_helpers import Linearizer
 from synapse.util.metrics import Measure
 
@@ -362,6 +362,20 @@ class ApplicationServicesHandler:
                             service, "to_device", new_token
                         )
 
+                    elif stream_key == "device_list_key":
+                        device_list_summary = await self._get_device_list_summary(
+                            service, new_token
+                        )
+                        if device_list_summary:
+                            self.scheduler.enqueue_for_appservice(
+                                service, device_list_summary=device_list_summary
+                            )
+
+                        # Persist the latest handled stream token for this appservice
+                        await self.store.set_appservice_stream_type_pos(
+                            service, "device_list", new_token
+                        )
+
     async def _handle_typing(
         self, service: ApplicationService, new_token: int
     ) -> List[JsonDict]:
@@ -568,6 +582,98 @@ class ApplicationServicesHandler:
 
         return message_payload
 
+    async def _get_device_list_summary(
+        self,
+        appservice: ApplicationService,
+        new_key: int,
+    ) -> DeviceLists:
+        """
+        Retrieve a list of users who have changed their device lists.
+
+        Args:
+            appservice: The application service to retrieve device list changes for.
+            new_key: The stream key of the device list change that triggered this method call.
+
+        Returns:
+            A set of device list updates, comprised of users that the appservices needs to:
+                * resync the device list of, and
+                * stop tracking the device list of.
+        """
+        # Fetch the last successfully processed device list update stream ID
+        # for this appservice.
+        from_key = await self.store.get_type_stream_id_for_appservice(
+            appservice, "device_list"
+        )
+
+        # Fetch the users who have modified their device list since then.
+        users_with_changed_device_lists = (
+            await self.store.get_users_whose_devices_changed(
+                from_key, user_ids=None, to_key=new_key
+            )
+        )
+
+        # Filter out any users the application service is not interested in
+        #
+        # For each user who changed their device list, we want to check whether this
+        # appservice would be interested in the change.
+        filtered_users_with_changed_device_lists = {
+            user_id
+            for user_id in users_with_changed_device_lists
+            if await self._is_appservice_interested_in_device_lists_of_user(
+                appservice, user_id
+            )
+        }
+
+        # Create a summary of "changed" and "left" users.
+        # TODO: Calculate "left" users.
+        device_list_summary = DeviceLists(
+            changed=filtered_users_with_changed_device_lists
+        )
+
+        return device_list_summary
+
+    async def _is_appservice_interested_in_device_lists_of_user(
+        self,
+        appservice: ApplicationService,
+        user_id: str,
+    ) -> bool:
+        """
+        Returns whether a given application service is interested in the device list
+        updates of a given user.
+
+        The application service is interested in the user's device list updates if any
+        of the following are true:
+            * The user is the appservice's sender localpart user.
+            * The user is in the appservice's user namespace.
+            * At least one member of one room that the user is a part of is in the
+              appservice's user namespace.
+            * The appservice is explicitly (via room ID or alias) interested in at
+              least one room that the user is in.
+
+        Args:
+            appservice: The application service to gauge interest of.
+            user_id: The ID of the user whose device list interest is in question.
+
+        Returns:
+            True if the application service is interested in the user's device lists, False
+            otherwise.
+        """
+        # This method checks against both the sender localpart user as well as if the
+        # user is in the appservice's user namespace.
+        if appservice.is_interested_in_user(user_id):
+            return True
+
+        # FIXME: This is quite an expensive check. This method is called per device
+        #  list change.
+        room_ids = await self.store.get_rooms_for_user(user_id)
+        for room_id in room_ids:
+            # This method covers checking room members for appservice interest as well as
+            # room ID and alias checks.
+            if await appservice.is_interested_in_room(room_id, self.store):
+                return True
+
+        return False
+
     async def query_user_exists(self, user_id: str) -> bool:
         """Check if any application service knows this user_id exists.