Richard Hamming (from "You and Your Research", http://www.paulgraham.com/hamming.html):
1. What are the most important problems in your field?
2. Are you working on one of them?
3. Why not?
Paul Graham's (from "Good and Bad Procrastination", http://www.paulgraham.com/procrastination.html) generalization of Richard Hamming: What's the best thing you could be working on, and why aren't you?
edw519's generalization of Paul Graham: Work on the most important thing until it's not the most important thing any more.