Depending on your setup, this might be a troublesome one to figure out. You won't see any error emails coming through since it doesn't hit Django code yet, just 500 error page when trying to view the website.
With the changes to the WSGI code in Django, some of us may have forgotten to update the WSGI dispatcher which is needed to glue our project to the HTTP server.
To fix the error, you'll need to open up your WSGI dispatcher file and change the following lines:
application = django.core.handlers.wsgi.WSGIHandler()
from django.core.wsgi import get_wsgi_application
application = get_wsgi_application()
That should ensure that everything is smooth sailing again.