Creator Backlash: During the show's own theme song, no less! It's understandable however as the staff and cast did not approve of this change in direction from the outset.
Creator Killer: This series ended the Steven Spielberg presents series of cartoons and also caused many of the writers and producers (like Tom Ruegger, Sherri Stoner, and Paul Rugg) to not get any work for at least a few years.
Executive Meddling: The only reason this Re Tool even exists. The theme song explicitly states, "It's what the network wants, why bother to complain?", as Pinky and the Brain get kicked out of the Warner Brothers studio lot. At the end of the song, Brain says "I deeply resent this."
Franchise Killer: Before the Re Tool, Pinky and the Brain was a mega hit shown on prime time. Five episodes later, it was cancelled. It also wound up being the final collaborative work between Warner Bros. Animation and Amblin Entertainment as a result.
Old Shame: Nearly everyone who worked on this thing (Maurice LaMarche (The Brain), Rob Paulsen (Pinky), the writers) hated it with a passion. So much so that the theme song takes pot shots at the idea.
Ben Stein guest stars in "At the Hop" as "Rockin' Johnny Hot."
Tim Curry plays an evil carnival barker in "Teleport a Friend".
Technology Marches On: One episode has Brain planning to switch the background music of an amusement park ride with a subliminal message he recorded using audio cassettes as the medium. At the time the series aired, tapes were experiencing their last breath in the mainstream media.
Too Soon: "A Walk in the Park" has a parody of Shari Lewis and Lamp Chop (called Marie Flewis and Pork Chop) that was somehow left intact considering Lewis passed away six months before the episode aired.
Writer Revolt: The writers were extremely dissatisfied with the Executive Meddling they had to endure. Peter Hastings not only wrote the episode "You'll Never Eat Food Pellets in This Town Again", but later left Warner Bros. altogether to create Disney's One Saturday Morning.