"What's up?" means roughly the same as "How are you?". Does that help?

Chris is right. Here's some more detail. You don't answer it the same as "How are you?". "How are you" you respond with how you are feeling, for example "Good" or "Fine". "What's up" is asking "What have you been doing lately". Typical answers are "Not much" or "nothing". You can say things like "Just been working" but people don't want answers longer then that. "Hey man, what's up?" "Not much, what's up with you?" "Not a whole lot" "What's up" can also be a response to getting someone's attention. It means "Go ahead". John enters Bob's office and says "Hey Bob, I got a question for you" Bob: "What's up?" John asks question