A phrase used to ask about something odd, or what the point of something is. The word "that" can also be replaced with whatever noun the person is asking about. It is also common to inerject the word "fuck" into the phrase to express shock or discust.
What's up with the smirk?
Look at all those bags on the road. What's up with that?

Person1: What the fuck's up with your hand!?
Person2: Ahh! Why are you just standing there?! Take me to the fucking hospital!
by Cinymin86 November 16, 2009
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Whats up with me and you. When are you gonna let me get some.
Boy: Ayo, Whats up with the whats up?
Girl: Fuck outta here, I got a man. No Single Ladies shit.
Boy: ....Fraud.
by Ctfu February 10, 2010
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Meaning that you fully understand and/or agree and find yourself excited about the idea or suggestion proposed.
Friend 1: "Yeah so I'm thinking we chill before, and then hit the club by 9. Got mad beer at the crib anyway"
Friend 2: "That's what's up"
by KelsBels April 05, 2008
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What is happening wiht you, How are you, whats going on?
Something that LouAnn doesnt understand.

Usual response: Nothin Much
**Do not reply 'HI' or with another 'Whats Up'**

A common phrase that most people understand & use each day.
Carl: Hey Dude
Mark: Hey Whats up?
Carl: nothin much
Mark: Cool
by Ednabrowneye13 January 17, 2009
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An excuse for your friends to be dickwad punsters when you just want to hang out.
A-Hey what's up?
B-The sky!! hehehehe
A-Fuck you, Thomas
by j00j00 May 28, 2015
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A question that means "hi" or "What are you doing"
It can get annoying, but people don't seem to understand that.
The best way to answer is "I think it's the opposite of down" if you are annoyed by this question
by The Billionth Random Monkey December 15, 2014
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