When can I say "what is up with that?"?
The expression "what is up with that" normally expresses that something is crazy or ridiculous. It can be used either whenever you want an explanation for something or as a hypothetical question to indicate that something is crazy, but not for the purpose of receiving an answer. Ex: "I have been working late every night this week." "What is up with that?" Ex: What is up with this weather lately? It's been so hot! In the second example, "what is up with that" is a hypothetical question and is asked just to express that the weather has been unusual, but is not asked expecting a response or an explanation.