1. Short for "How are you doing?" It can also be used for the pickup variety of that question, "How you doin'? ;-)"
2. Also short for "How did you do?"
Guy: How you do? Baby.
Girl: OMG, where did you learn how to speak? That's your pickup line? hahahaha
You: How you do?
Guy: I used the line that you told me, but she laughed at me. That was so messed up.