Mac: Previously mentioned (and previously free) TuneSpan -- the app that splits your iTunes library across multiple drives -- is on sale right now for $1.99, down from its usual $15.49 asking price. If you have a large music collection that won't fit on your primary drive, this app will solve your problem.
TuneSpan looks a lot like iTunes when you open it up, making it a familiar way to set locations for your music. You simply pick the files you want to move and choose a drive to put them on. TuneSpan then updates your iTunes library file so iTunes knows to look for the files elsewhere. While you will need to have the drive connected in order to access the files you can put the music you play less elsewhere and just connect the drive when you need it. This way you can have one giant library without taking up an enormous amount of disk space.