Are you seeing this error in your logs: [NSCFString characterAtIndex:]: Range or index out of bounds? If so, it may be a problem with your fonts. Fontbook is a a great way to manage your fonts, but don't be fooled into thinking it's the end-all and be-all of font management systems.
DON'T drag a folder of 5000 fonts into Fontbook and expect things to work. Most applications have a hard-set limit as to how many fonts they can work with, and many (including Apple's iChat, Mail, and Safari) will behave oddly or downright crash if the font database is overloaded. The error above is a result of this overloading. Use Fontbook's Enable/Disable buttons to keep most of your fonts offline. Make custom collections of the fonts you need for your projects, and only bring one online at a time.
Another problem isn't so much due to Fontbook the application as it is the ATSServer system resource. ATSServer is responsible for notifying running applications that the fonts available have changed. If you have a half dozen programs running and drop a folder of 700 fonts into Fontbook, ATSServer will notify each app, for each font. This will take a long time and eat lots of CPU cycles, but worse than that, some apps (like one or more of the three above) start to eat memory and virtual memory on your hard drive. It ate the remaining 6GB on my machine and still wanted more. Make SURE you close all running applications before installing that many fonts at once, and then only install a hundred or so at a time (because Finder and Fontbook, at least, will still be running).
[robg adds: A previous hint explains another possible cause of the Range or index out of bounds error message.]
Mac OS X Hints
http://hints.macworld.com/article.php?story=20040113020917306