diff --git a/datasette/app.py b/datasette/app.py
index ebab3bee..ca2efa91 100644
--- a/datasette/app.py
+++ b/datasette/app.py
@@ -302,6 +302,13 @@ class Datasette:
         self._permission_checks = collections.deque(maxlen=200)
         self._root_token = secrets.token_hex(32)
 
+    async def invoke_startup(self):
+        for hook in pm.hook.startup(datasette=self):
+            if callable(hook):
+                hook = hook()
+            if asyncio.iscoroutine(hook):
+                hook = await hook
+
     def sign(self, value, namespace="default"):
         return URLSafeSerializer(self._secret, namespace).dumps(value)
 
diff --git a/datasette/cli.py b/datasette/cli.py
index ff9a2d5c..bba72484 100644
--- a/datasette/cli.py
+++ b/datasette/cli.py
@@ -397,6 +397,9 @@ def serve(
         # Private utility mechanism for writing unit tests
         return ds
 
+    # Run the "startup" plugin hooks
+    asyncio.get_event_loop().run_until_complete(ds.invoke_startup())
+
     # Run async sanity checks - but only if we're not under pytest
     asyncio.get_event_loop().run_until_complete(check_databases(ds))
 
diff --git a/datasette/hookspecs.py b/datasette/hookspecs.py
index ab3e131c..9fceee41 100644
--- a/datasette/hookspecs.py
+++ b/datasette/hookspecs.py
@@ -5,6 +5,11 @@ hookspec = HookspecMarker("datasette")
 hookimpl = HookimplMarker("datasette")
 
 
+@hookspec
+def startup(datasette):
+    "Fires directly after Datasette first starts running"
+
+
 @hookspec
 def asgi_wrapper(datasette):
     "Returns an ASGI middleware callable to wrap our ASGI application with"
diff --git a/docs/plugins.rst b/docs/plugins.rst
index 608f93da..289be649 100644
--- a/docs/plugins.rst
+++ b/docs/plugins.rst
@@ -995,6 +995,39 @@ This example plugin adds a ``x-databases`` HTTP header listing the currently att
 
 Examples: `datasette-auth-github <https://github.com/simonw/datasette-auth-github>`_, `datasette-search-all <https://github.com/simonw/datasette-search-all>`_, `datasette-media <https://github.com/simonw/datasette-media>`_
 
+.. _plugin_hook_startup:
+
+startup(datasette)
+~~~~~~~~~~~~~~~~~~
+
+This hook fires when the Datasette application server first starts up. You can implement a regular function, for example to validate required plugin configuration:
+
+.. code-block:: python
+
+    @hookimpl
+    def startup(datasette):
+        config = datasette.plugin_config("my-plugin") or {}
+        assert "required-setting" in config, "my-plugin requires setting required-setting"
+
+Or you can return an async function which will be awaited on startup. Use this option if you need to make any database queries:
+
+    @hookimpl
+    def startup(datasette):
+        async def inner():
+            db = datasette.get_database()
+            if "my_table" not in await db.table_names():
+                await db.execute_write("""
+                    create table my_table (mycol text)
+                """, block=True)
+        return inner
+
+
+Potential use-cases:
+
+* Run some initialization code for the plugin
+* Create database tables that a plugin needs
+* Validate the metadata configuration for a plugin on startup, and raise an error if it is invalid
+
 .. _plugin_hook_actor_from_request:
 
 actor_from_request(datasette, request)
diff --git a/tests/fixtures.py b/tests/fixtures.py
index 907bf895..09819575 100644
--- a/tests/fixtures.py
+++ b/tests/fixtures.py
@@ -49,6 +49,7 @@ EXPECTED_PLUGINS = [
             "register_facet_classes",
             "register_routes",
             "render_cell",
+            "startup",
         ],
     },
     {
diff --git a/tests/plugins/my_plugin.py b/tests/plugins/my_plugin.py
index a0f7441b..3f019a84 100644
--- a/tests/plugins/my_plugin.py
+++ b/tests/plugins/my_plugin.py
@@ -167,3 +167,8 @@ def register_routes():
         (r"/two/(?P<name>.*)$", two),
         (r"/three/$", three),
     ]
+
+
+@hookimpl
+def startup(datasette):
+    datasette._startup_hook_fired = True
diff --git a/tests/test_cli.py b/tests/test_cli.py
index 6939fe57..90aa990d 100644
--- a/tests/test_cli.py
+++ b/tests/test_cli.py
@@ -10,6 +10,7 @@ from click.testing import CliRunner
 import io
 import json
 import pathlib
+import pytest
 import textwrap
 
 
diff --git a/tests/test_plugins.py b/tests/test_plugins.py
index 0fae3740..c0a7438f 100644
--- a/tests/test_plugins.py
+++ b/tests/test_plugins.py
@@ -572,3 +572,9 @@ def test_register_routes_asgi(app_client):
     response = app_client.get("/three/")
     assert {"hello": "world"} == response.json
     assert "1" == response.headers["x-three"]
+
+
+@pytest.mark.asyncio
+async def test_startup(app_client):
+    await app_client.ds.invoke_startup()
+    assert app_client.ds._startup_hook_fired