I learned today that you cannot send an email to an email address not in your lead database.
My Use Case: I had a filter set to 'Email Address is email@example.com', however as this email was not in my lead database, it would not add to the smart list. In this case, I just wanted to include someone for a one-time email, not necessarily add them to my database to receive emails going forward.
So, my idea is... If you exlipcitly add a filter 'Email address is...', Marketo should add that email to your smart list regardless if that email is in your database or not.
(if your curious, I ended up adding the email to my database)