First season
During the first season, the show centered on the four teenagers as high school students and included guests such as Scott Foley as a college boy Zoe had a crush on, Sara Rue as a wheelchair-using bully, Will Friedle as a charming stoner who dated Zoe, and Jacinda Barrett as a girl who liked both Duncan and Jack.

The first season theme song was "Charmed" by My Friend Steve.

Second season
When the show returned for a second season, it had been heavily retooled. The friendship between the four friends remained intact, but now they were adult college students. Gone was Keller as Zoe's mom, while Omar Gooding joined the cast as the foursome's friend Doug Anderson. The title had also been shortened to simply Zoe... (pronounced on-air as Zoe Dot Dot Dot) out of fear that the former title was turning off potential viewers.

After the series was cancelled, Michael Rosenbaum expressed disappointment with the fact that the network had cut his character's name out of the title for the second season.