Kaz and Oliver learn that pranks do not exist in the world of their superhero friend Skylar, and they set out to teach her how to prank. When The Great Defender joins in, he takes the pranks too far and wreaks havoc on the hospital. Guest starring is NBA star Dwight Howard as The Great Defender.

When Gus contracts a strange illness, he develops formidable powers and turns evil. Kaz and Oliver devise a plan to sneak him into the ER for treatment, where they must figure out a way to cure their maniacal friend before he destroys everything in the hospital. Meanwhile, Horace pretends to be Skylar's father for her parent-teacher conference but gets overly carried away with the idea.