Since installing Tiger, I have moved my music collection onto an external FireWire hard drive, while keeping iTunes and my library files on the internal hard drive. I noticed frequent skipping in playback, and it was mostly in conjunction with a spike in the mdimport process (Spotlight indexing). Even though both my drives are already indexed, this brief re-indexing was causing the problem.
I managed to significantly reduce the skipping by disabling indexing on my FireWire drive (named 'Fire'):
sudo mdutil -i off /Volumes/Fire
I might also have to disable indexing on my internal drive, but the skips seem infrequent enough now.
Mac OS X Hints
http://hints.macworld.com/article.php?story=20050623234932431