EDIT: This answer applies if you want to change settings for a small number of specific tests.
Since Django 1.4, there are ways to override settings during tests:
https://docs.djangoproject.com/en/stable/topics/testing/tools/#overriding-settings
TestCase will have a self.settings context manager, and there will also be an @override_settings decorator that can be applied to either a test method or a whole TestCase subclass.
These features did not exist yet in Django 1.3.
If you want to change settings for all your tests, you’ll want to create a separate settings file for test, which can load and override settings from your main settings file. There are several good approaches to this in the other answers; I have seen successful variations on both hspander’s and dmitrii’s approaches.