The series is about three girls made out of sugar, spice, everything nice, and Chemical X to defend Townsville from all sorts of crime and evil, alongside daily lives before bedtime.
The show gained it origins as, surprisingly enough, a drawing that Craig had made for a birthday card. When it was pointed out how silly the girls look. He decided to make it into the subjects of his art student film, dubbing them the Whoopass Girls. After graduating and working his way through as a animator for Hanna-Barbera, he was given a chance to submit a cartoon pilot for the then fledgling Cartoon Network who were moving into producing their own works. Once again, he used the girls as his subject, re-christening them into the more kid-friendly Powerpuff Girls. The short was showcased on a Space Ghost Coast to Coast special which showcased these pilots (among which was also Dexter's Laboratory) and apparently "winning" it (if only because Craig was willing to dance in a silly get-up at Space Ghost's demand). Said pilot premiered on What A Cartoon! Show. After positive response to it, another short was commissioned and ultimately the series was green-lighted for a full blown series in 1998, gaining acclaim for both it's silly yet creative premise and willing the push the boundary of an animated show for kids. Becoming one of the flagship shows on the network in the late 90's and early 2000's. The original series lasted through 2005 through six seasons.
The franchise consists of 252 episodes, 10 seasons, 10 shorts, 4 specials, and 2 movies. Although the shows aired on US television for 12 years (14 if one counts The Powerpuff Girls Z which was aired outside the United States), the franchise is actually 20 years old since it was introduced on November 18, 1998.
- The Whoopass Girls in A Sticky Situation (1992): The original short, featuring prototype versions of the girls fighting the Amoeba Boys.
- Meat Fuzzy Lumpkins (1996) and Crime 101 (1997): Early concept shorts created for the What A Cartoon! Show animation anthology series.
- The Powerpuff Girls (1998) (1998-2005): The original series, centered on the comedy/action adventures of the titular characters. Lasted for 78 episodes.
- Powerpuff Girls Z (2006-2007): An anime adaptation of the original series produced by Aniplex. An alternate continuity wherein the girls are classmates who become magical girls after a laboratory accident causes citizens across New Townsville to mutate or gain superpowers. Lasted for 52 episodes and never aired in the United States despite receiving an English dub.
- The Powerpuff Girls (2016) (2016-2019): A Soft Reboot of the series with a more Slice of Life bent, produced by Bob Boyle and Nick Jennings with no involvement from McCracken.
- Powerpuff: An in-development pilot created by Greg Berlanti created for The CW announced in 2020. The series follows Blossom (Chloe Bennet), Bubbles (Dove Cameron), and Buttercup (Yana Perrault) in their 20s trying to have normal lives, resentful of losing their childhood to crimefighting. When the world is left in greater peril than ever before, the three girls are forced to reunite and work together again to save the day.
- The Powerpuff Girls Movie (2002): An origin story of the girls' creation, early days and how they became the protectors of Townsville. The first theatrical movie based on a Cartoon Network property.
- The Powerpuff Girls Rule!!! (2008): Created for the franchise's 10th anniversary, written and directed by Craig McCracken. Word of God considers this to be the Grand Finale for the original show.
- The Powerpuff Girls: Dance Pantsed (2014): A second special, directed by David P. Smith and the first Western Powerpuff Girls production to be done without McCracken's involvement. Featured Ringo Starr. Noted for being entirely CGI animated.
- TTG v PPG : A crossover between the 2016 series and Teen Titans Go!.
- DC Comics Issues (1999-2006)
- CN Block Party: Merged into this series along with other CN series after main comics ended, ended in 2009.
- IDW Comics Issues: Picked up the license from DC in 2012. Original six issue series followed. Along with publishing comics for the 2016 series
- Cartoon Network Super Secret Crisis War: Part of a crossover with Dexter's Laboratory, Samurai Jack, Ben 10 Omniverse and Ed, Ed and Eddy.
- Super Smash-Up: Another crossover which sees the girls visiting different dimensions inhabited by other CN shows.
- The Powerpuff Girls: Chemical X-Traction (2001) An arena fighter, similar in the vein of Power Stone (Playstation, Nintendo 64)
- The Powerpuff Girls: Relish Rampage (2002) (Playstation 2, Gamecube) A free roam action game.
- The Powerpuff Girls: Bad Mojo Jojo (2000) (Game Boy Color)
- The Powerpuff Girls: Paint the Townsville Green (2000) (Game Boy Color)
- The Powerpuff Girls: Battle HIM (2001) (Game Boy Color)
- The Powerpuff Girls: Mojo Jojo A-Go-Go (2001) (Game Boy Advance)
- The Powerpuff Girls: HIM and Seek (2002) (Game Boy Advance)
- Game de Demashita! Powerpuff Girls Z (lit Demashita! Powerpuff Girls Z: The Game) (2007) (Nintendo DS, never released outside of Japan)
- The Powerpuff Girls: Gamesville (2002)
- The Powerpuff Girls: Mojo Jojo's Clone Zone
- The Powerpuff Girls: Princess Snorebucks
- The Powerpuff Girls: Mojo Jojo's Pet Project
- The Powerpuff Girls: Defenders of Townsville
- Heroes & Villains (2000): An album featuring music inspired by the original show.
- Cartoon Network Racing (2006)
- FusionFall (2009): An MMO crossover with the girls making guest appearances.
- Cartoon Network: Punch Time Explosion (2011): A crossover fighting game with the girls as playable characters.
- LEGO Dimensions (2017): 2 packs consisting of a Team Pack and a Fun Pack renders all 3 girls playable, and an Adventure World adapting the show is also included. All of these are based on the 2016 series.