I've written before that crafting a satisfying career is an art as much as a science. Rachel at I Hate HR (and no, she doesn't really hate HR) demonstrates this art in her recent posting Know When to Fold ''Em. She discusses 4 signs that it may be time to look for a new job - even in a volatile economy.
I really like her point to leave when mentors and trusted advisors tell you to. She clarifies by saying:
"Don’t listen to your friends that will tell you to quit your job every time you complain. Listen to the trusted advisers who tell you when it’s in your best interest for your career for you to leave. If you don’t have someone like this in your life right now get one."
I would add that another good reason to leave is when you can no longer learn something new and grow in how you can contribute to an organization. This goes hand in hand with having good mentors who can help you figure out how you can best use your skills to make a positive difference.