Traditionally, a sign that everything is OK.
Or, if you're deaf, it means hello.

Or if you're Australian, it is more of a crocodile pacification technique.

If you're a Roman Emperor, it means, "Okay gladiator one, you can let gladiator two live." The opposite gesture, thumbs-down, means, "Gladiator two bores me. I'd rather watch carrion feast on his flesh than watch him fight and lose again."