Cartoon Network asked for a seventh season of the series. Creators and producers Craig McCracken and Chris Savino felt that six was enough.
George Jetson of The Jetsons (1962) occasionally appears in the background flying in his space car as Blossom, Bubbles, and Buttercup are in flight to a rescue.
The devilish, demonic rival named is referred to as "Him" because the producers thought the Devil or Satan or any other name would be too controversial for a kids' show.
All of the character designs are based around curves with exception of one. Professor Utonium's design is based entirely around straight lines and sharp angles.
The Powerpuff Girls (1998) names were based on Flora, Fauna and Merryweather from the popular Walt Disney Animation Studios animated movie Sleeping Beauty (1959).