The show was cancelled prematurely due to a writer's strike that occurred during the 2007-2008 TV season. Once the writer's strike ended, CW chose not to extend the series since it already wasn't going to be renewed another season. This left fans with several cliffhangers for each of the main characters.

Flex Alexander portrayed Darnell Wilkes during the first season. However, once he got the role on the show One on One he left the show and Darnell was portrayed by Khalil Khan for the rest of the series.

An unaired pilot episode was filmed with two different actresses portraying main characters. Leslie Silva and Christina Cox played Toni Childs and Lynn Searcy, respectively. Clips from the original pilot could be seen during commercials advertising the 2000-2001 lineup of shows to air on UPN Monday nights. By the time the show premiered, however, Jill Marie Jones had replaced Leslie Silva as Toni, Persia White had replaced Christina Cox as Lynn, and the original pilot never aired.

Although both Tracee Ellis Ross (Joan) and Persis White (Lynn) are both bi-racial, only Lynn is biracial in the series.

Tracee Ellis Ross is the only cast member to appear in every episode of the series.

Three of the four leads wore braces beginning season three (Lynn [Persia White], Maya [Golden Brooks], and Jill Marie Jones [Toni]).

Golden Brooks originally auditioned for the character Toni Childs, not Maya Wilkes, the character she would eventually portray on the series.

Jill Marie Jones left the series in 2006 due to her contract expiring and the desire to explore other options - movies in particular.

Girlfriends was one of the highest-rated scripted shows on television among African-American adults 18-34, including its spin-off The Game (2006).

The running gag in the series is Maya (Golden Brooks) is the youngest of the group, and Toni (Jill Marie Jones) is the eldest (she had to repeat a grade in elementary school). However, Jill Marie Jones (Toni) is the youngest (b. January 4, 1975), then Tracee Ellis Ross (Joan) (b. October 29, 1972) next Persia White (Lynn) (b. October 25, 1972, and lastly Golden Brooks (Maya) (b. December 1, 1970).

Has a spin-off series, The Game (2006).

The final episode aired on February 11, 2008.

Tracee Ellis Ross won the 2009 NAACP Image Award in the Outstanding Actress in a Comedy Series category for her role as Joan Clayton in Girlfriends (2000).

When Girlfriends returned in fall 2007 for its eighth season, it became the longest-running live-action sitcom on network television that was on air during that time.

After the sixth season, the show was picked up by The CW because UPN merged with The WB to form The CW.

Khalil Kain character of Darnell is supposed to have been in highschool with Maya, but in real life they are 6 years apart in age.

Tracee Ellis Ross (Joan Clayton) & Jenifer Lewis (Veretta Childs) also worked together on Black-ish (2014) as Rainbow Johnson & Ruby respectively.

Reginald C. Hayes won the 2005 NAACP Image Award in the Outstanding Supporting Actor in a Comedy Series category for his role as William Jerome Dent in Girlfriends (2000).

Girlfriends is an American sitcom that premiered on September 11, 2000, on UPN and aired on UPN's successor network, The CW, before being cancelled in 2008.

Reginald C. Hayes won the 2006 NAACP Image Award in the Outstanding Supporting Actor in a Comedy Series category for his role as William Jerome Dent in Girlfriends (2000).

Tracee Ellis Ross won the 2007 NAACP Image Award in the Outstanding Actress in a Comedy Series category for her role as Joan Clayton in Girlfriends (2000).

William's middle name is actually spelled JERROWME (still pronounced Jerome). This was revealed in the episode when he and Yvonne were getting married but she hadn't met his mother yet.