A shortened version of "What's up", which replaces greetings such as "Hello", "How are you?", "What's going on?", etc. This phrase was possibly made popular in the 1940's from a cartoon called Bugs Bunny, when the rabbit said his famous catch phrase, "Eh...What's up, doc?".
If you are not a social recluse then you will most likely be asked "Whatsup?" multiple times a day and be expected to answer with the vague "nothin", "not shit", "chillin", etc.
Other ways to say whatsup:
How's it hanging?, How ya derrin?, How ya doin?, What ho, What it be?, What it do?, What it is?, What's clickin?, What's crackin'?, What's poppin?, What's new?, What gives?, What's cookin?, What's crackalackin?, What's happenin?, etc.
Bob- Hey girl, whatsup?
Lucy- The sky!
Bob- (Smart ass...)
Bob- Hey man, whatsup?
Jones- Not shit man.