The series focuses on the lives of Hefner's three girlfriends who live with him at the Playboy Mansion: Holly Madison, Bridget Marquardt, and Kendra Wilkinson. Hefner, various Playmates, and other celebrities sometimes make guest appearances.

The series not only showcases events at the Playboy Mansion (e.g. Fight Night, 4th of July celebration, etc.), but also sheds light on other Playboy related events such as the Playboy Jazz Festival at the Hollywood Bowl, Playmate test shoots at Playboy Studio West, Operation Playmate, pillow fights, party night, birthday parties, etc.

To celebrate the success of the series, Playboy published a special nude pictorial of Holly, Bridget, and Kendra in the November 2005 issue. The original eight-episode run of the series was expanded to fifteen episodes with the first season finale airing in early December 2005. The series' second season began on July 30, 2006. To celebrate the launch of the second season, a second nude pictorial of the trio was published in September 2006. The third season of the show began airing March 4, 2007.

The show's theme song is Nasty Tales's remix of "Come on-a My House".

• The Girls Next Door at E!
• The Girls Next Door at Playboy.com