Can I use the same Time Machine drive with OS X 10.5 and 10.8? I have an external 500 GB hard drive that I used to use for Time Machine backups with my PowerBook G4 running OS X 10.5 (Leopard). However, I now use it with a white MacBook running 10.8 (Mountain Lion). The PowerBook backups are still on the drive (each machine gets its own directory by default), but I have not backed up the PowerBook since I started using the drive with the MacBook.

My question is, is it safe to do a backup of the PowerBook again? Does Time Machine in Mountain Lion do anything differently to the drive that would make it not work correctly with Leopard, or vice versa?

I ask because the PowerBook is finally failing (occasionally boots directly to a kernel panic) so I'd like to do one last backup before it bites the dust.
Yes - whether you have a USB or other direct drive or a network drive, Time Machine will cooperate with different Mac backing up to the same destination. 

The only problem would be if you enabled FileVault on a direct attached drive since only Lion and later can read those.