Select all your open fonts in font book
File >> validate fonts
You can still preview fonts in font book, even though they are not open, just ctrl click on them and choose disable to grey them out. Your apps will boot much faster, and you will have fewer problems if you can disable the fonts you do not use often.
Since now I know you are on mac, you can find all your .lst files and delete them to clean up your font cache.
If you want to clean/speed up your fonts even more remove the foreign language fonts using the free monolingual utilty. Drive Genius 3 is a commercial app, but does a fantastic job of removing GB's of hidden foreign language files and libraries using the drive slim feature.
