"What's up?" means "What's happening?" or "What's going on?" So you can answer this question politely by saying something like "I'm going to school." It could also mean "What's wrong?" or "What do you want to talk about?" For example, if I get a voicemail message from a friend who says she wants to talk, I would call her back and say "Hey, what's up?" Then she can start talking about whatever ...