When a demon escapes from custody, Agent Murphy enlists the Charmed Ones to help, where they learn a government created virus is spreading amongst magical beings, that causes them to "hulk out". Meanwhile, Billie becomes infected with the virus and it's up to the sisters to find an antidote.

Paige learns the difficulties of dating a mortal when Henry becomes too involved in the magical world and is torn when another suitor arrives hoping to convince her to marry him so they can become the ultimate magical couple. Meanwhile, Billie finally finds her missing sister, Christy; Piper faces a romantic decision when she runs into an old flame and begins to wonder if she should move on with her life.