Even though they'll likely find someone to replace him, when the lead of your core developer team quits, one can safely say that your project's headed out to pasture. That's exactly what just went down with Mambo, where the fight over open source led to the split of the development community last year, giving rise to Joomla.

"Miro International is continuing to lose developers in its attempt to maintain control of its 'open-source' Mambo CMS (content management system). Now, Mambo's core development team leader Martin Brampton has called it quits."