The bosses will always return. They're there to play again and again. I was excited when I found that out; I wanted two ultima weapons. Unfortunately, the ultima weapon chest can only be opened once. The same goes for a lot of the key chests, but all the rest are free for the taking time and again. Stuff like red fangs and blue fangs, elixers, even megalixers can be found over and over. But the chests that return are usually randomly filled.

Some of the bosses drop items, you know. If you check them out in your bestiary, you might find an item or two listed that'll make you want to battle a particular boss again.