Monsters are creatures that come in many shapes and sizes. A vast majority of them are giant, grotesque and/or destructive. Occasionally Townsville is attacked by monsters and it is up to the Powerpuff Girls to stop them.

Despite their fearsome appearance and destructive nature, a lot of monsters are intelligent and sometimes have a reason for destroying Townsville. Some monsters who survive being defeated by the Powerpuff are regarded as heroes amongst other monsters. Most monsters come from Monster Isle, a small island fairly close to Townsville's shore. They are largely based on the Kaiju, giant monsters of Japanese popular culture that can be either good or evil towards mankind.