A close second is the job you have is the one you hate. Whether its the work, the company or the boss. According to Dilbert creator Scott Adams in a recent WSJ article:
"Our system requires a continuous supply of highly capable people who are so disgruntled with their jobs that they are willing to chew off their own arms to escape their bosses. The economy needs hamster-brained sociopaths in management to drive down the opportunity cost of entrepreneurship. Luckily, we're blessed with an ample supply." Read the full article
Either way, find something you love, make a plan, count your pennies (use open source erp) and go out and make it happen. You might not be a success the first time out, so you take the lessons learned and make another run at it.