I use a waterproof mattress pad. I think I bought it at Buy Buy Baby. The clerks there -- or at any baby store -- would be able to help you find one. (In addition to protecting your mattress from bodily fluids, I think it makes it a little less cold than just a sheet.) Then I put on the sheet, and then I often put a breakaway sheet on TOP of the pretty sheet.
The breakaway sheet is plain white, but I especially liked having it when I used a crib bumper because man, did that thing make the crib a pain to change! I'd just pull off the breakaway sheet after a few days (or a poop explosion) and have the cute sheet for a few days before I had to take the whole thing apart to wash the cute sheet. I don't always use the breakaway sheet, but I was really glad I had it in the closet when my son came down with the stomach flu a few months ago and we went through several sets of bedding in a night!
In short, I think you need a waterproof mattress cover. The breakaway sheet is optional, but handy.
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