Recently I installed several hundred fonts in one fell swoop. This was a mistake, because all my apps slowed down (especially Microsoft Office). While the fonts are useful, and I needed to keep them, I needed them only for DTP. My mistake was to install them to the computer, rather than just the user account I use for DTP.
I tried using various font management apps to move them across to the user account but I wasn't sure which fonts were the new ones, compared to the old or System fonts.
The solution was to dig into /Library/Fonts/ and sort the files by date. Sure enough, the new fonts had the same creation date and I was able to manually drag them across to my own ~/Library/Fonts/ folder.
After a quick flush of the font cache, everything is back to normal and my system speed has been restored. Other user accounts now work perfectly.
[crarko adds: I've had to do similar things for clients of mine, and yes it can be a pain. This hint covers clearing the font cache for Leopard and Snow Leopard, and this one is for Tiger. There are also a number of third party utilities that can do this.]
Mac OS X Hints
http://hints.macworld.com/article.php?story=20100817095715567