Find the intersection of something that you think will be inevitable in the future and huge, and something that gets you out of bed in the morning.

That's the advice Mark Shuttleworth gave a friend of mine.  His example was that he was in the early days of the web and he realized that secure commerce on the internet would be needed.  And he figured out a way to do that.  Made a CA and sold it to verisign for 500M and then started Ubuntu.