The story of David Hobbs, who has spent the last decade playing the perfect father on one of TV’s biggest sitcoms. But when the series ends and his wife resumes her own television career, he finds himself cast in his most challenging role to date: handling the day-to-day needs of three kids who've grown accustomed to not having him around. David soon learns that playing a dad on TV is child’s play compared to the real thing.

Glenn Martin, DDS is an American-Canadian stop-motion-animated television series that premiered on Nick at Nite on August 17, 2009. The series was produced by Tornante Animation in association with Cuppa Coffee Studio. Glenn Martin, DDS was Nick at Nite's fourth original series.

The show premiered on March 18, 2010 on Sky1 in the UK and Ireland. Season two premiered on June 11, 2010. The show ended on November 7th, 2011.

Fatherhood is an American animated television series revolving around the Bindlebeep family and various happenings, inspired by the book of the same name by Bill Cosby. This was Nick at Nite's first original animated series. It has aired on Nick at Nite and Nickelodeon. It was canceled in 2005.

Martini Mondays and tequila Tuesdays take a back seat to new step-motherhood when former party girl Stephanie marries Charlie, an older dad with three kids. Becoming an instant mom doesn't come with a rulebook, but it does come with a dose of humor as Stephanie traverses the fine line between being a friend and being a responsible parent.

Loren (Brittany Underwood) a smart, shy and independent high school senior who has ambitions of being a songwriter, secretly sends her song lyrics to her celebrity crush, rock superstar Eddie Duran (Cody Longo). Loren's wildest dreams come true when she not only wins a songwriting competition sponsored by Eddie, but strikes up a friendship with her idol. Eddie sees beyond Loren's potential as a songwriter and gives her a first break as a singer, and when the truth about his less-than-faithful girlfriend Chloe (Melissa Ordway) is revealed, Eddie and Loren's friendship blossoms.

Hi-Jinks is a hidden camera show that premiered on Nick at Nite in 2005. The show is hosted by Leila Sbitani. The show gives parents a chance to play practical jokes on their children, in a similar fashion to Candid Camera. Taking a cue from Punk'd, each show features a prank that is conducted with the assistance of a known celebrity.

On the Television is the cable network Nick at Nite’s first attempt at original late-night programming. The sketch comedy show, can be described as a satirical television critic show in the style of Siskel and Ebert. The one line pitch was "a fake Siskel and Ebert reviewing fake TV shows." It starred Tim Conway Jr. and George McGrath as Dan Clark and Kevin Rush respectively. The show began as an April Fool’s Day Special for Nick-at-Nite with Taylor Negron co-hosting with McGrath.