If you don't want to manage multiple music libraries and would rather just have one, but your iTunes is eating up precious disk space, TuneSpan can migrate your excess media to external drives while still keeping it accessible within iTunes. This way you can move music you don't listen to very often to an external drive and just plug it in when you want to access the files.
TuneSpan makes this possible by copying the files to a designated external drive and updating your iTunes music library file to contain the new locations. Technically you could do this manually, but it would be really tedious and a waste of time. The only time you'll run into a problem is if your iTunes library isn't in its default location. You can, of course, remedy this by creating a symlink.
Using the program is a lot like using iTunes. They look alike and that makes it really easy to find what you want to move around. When you've got some content you want to move to another drive, just select it and click the "Span..." button. You'll need to set a spanning location for this to work, which you can do by dragging a folder on to the bottom bar or just clicking it to browse to the location you want.
TuneSpan is a free app for Mac OS X 10.5 or higher, but they definitely let you know very clearly that they appreciate donations — so help them out if you like it.