Yakko, Wakko and Dot return for all-new big laughs and the occasional epic takedown of authority figures in serious need of an ego check. Joining the Warners are Starbox & Cindy on their latest play date while Pinky and the Brain's ideas for world domination lead them to all new adventures.

Pinky and Brain are genetically enhanced laboratory mice who reside in a cage in the Acme Labs research facility. Brain is self-centered and scheming; Pinky is good-natured but feebleminded. In each episode, Brain devises a new plan to take over the world, which ultimately ends in failure, usually due to Pinky's idiocy, the impossibility of Brain's plan, Brain's own arrogance, or just circumstances beyond their control.