While working on MADtv, Borstein met Seth MacFarlane, who was then preparing to launch the animated sitcom Family Guy on FOX.
MacFarlane was originally supposed to create animated shorts for MADtv, but declined in favor of creating an independent series.
MacFarlane cast Borstein as the voice of character Lois Griffin.
After the show's debut in January 1999, Family Guy was cancelled by the network in 2002, but returned in 2005.
As well as her role as the voice performer for Lois and several other characters (including a brief appearance as Ms. Swan in a 2005 episode), she is also a producer and staff writer.
She was nominated for a Primetime Emmy Award for Outstanding Voice-Over Performance for the episode "Lois Comes Out of Her Shell" in 2013.

In 2000, Borstein was cast as Sookie St. James in the WB drama Gilmore Girls.
She portrayed Sookie in the pilot, but her MADtv contract prevented her from continuing in the role, which was recast with Melissa McCarthy.
Borstein made recurring appearances on Gilmore Girls throughout the show's run, first as the harpist Drella and later as the stylist Miss Celine.

As a film actress, she played the school principal in The Lizzie McGuire Movie (2003), the best friend of Halle Berry's character in Catwoman (2004), and an employee at CBS News in Good Night, and Good Luck (2005).
She also had a small role in the movie Bad Santa (2003) and an uncredited cameo as an obnoxious coffee shop patron in the Will Ferrell movie Kicking & Screaming (2005).
On some commercials, she sometimes voices Olive Oyl from Popeye and Betty Boop.

Borstein was a co-host of GSN's Celebrity Blackjack in 2004.
She made at least three guest appearances, once as Lois Griffin, on the Comedy Central animated program Drawn Together.

Borstein was cast as a press secretary in the 2007 sitcom pilot The Thick of It, but the series was not picked up for broadcast.
She was seen in the 2009 comedy For Christ's Sake, which was directed by her then husband Jackson Douglas.

Borstein's production company is called Crackerpants, Inc. In 2007, they released the DVD Drop Dead Gorgeous (in a Down-to-Earth Bombshell Sort of Way), a recording of a live performance at the Alex Theatre, with opening act Teddy Towne.
The title comes from one of many actual female character breakdowns Borstein reads from to illustrate sexism in the industry.
While working on MADtv, Borstein met Seth MacFarlane, who was then preparing to launch the animated sitcom Family Guy on FOX. MacFarlane was originally supposed to create animated shorts for MADtv, but declined in favor of creating an independent series. MacFarlane cast Borstein as the voice of character Lois Griffin. After the show's debut in January 1999, Family Guy was cancelled by the network in 2002, but returned in 2005. As well as her role as the voice performer for Lois and several other characters (including a brief appearance as Ms. Swan in a 2005 episode), she is also a producer and staff writer. She was nominated for a Primetime Emmy Award for Outstanding Voice-Over Performance for the episode "Lois Comes Out of Her Shell" in 2013.
In 2000, Borstein was cast as Sookie St. James in the WB drama Gilmore Girls. She portrayed Sookie in the pilot, but her MADtv contract prevented her from continuing in the role, which was recast with Melissa McCarthy. Borstein made recurring appearances on Gilmore Girls throughout the show's run, first as the harpist Drella and later as the stylist Miss Celine.
As a film actress, she played the school principal in The Lizzie McGuire Movie (2003), the best friend of Halle Berry's character in Catwoman (2004), and an employee at CBS News in Good Night, and Good Luck (2005). She also had a small role in the movie Bad Santa (2003) and an uncredited cameo as an obnoxious coffee shop patron in the Will Ferrell movie Kicking & Screaming (2005). On some commercials, she sometimes voices Olive Oyl from Popeye and Betty Boop.
Borstein was a co-host of GSN's Celebrity Blackjack in 2004. She made at least three guest appearances, once as Lois Griffin, on the Comedy Central animated program Drawn Together.
Borstein was cast as a press secretary in the 2007 sitcom pilot The Thick of It, but the series was not picked up for broadcast. She was seen in the 2009 comedy For Christ's Sake, which was directed by her then husband Jackson Douglas.
Borstein's production company is called Crackerpants, Inc. In 2007, they released the DVD Drop Dead Gorgeous (in a Down-to-Earth Bombshell Sort of Way), a recording of a live performance at the Alex Theatre, with opening act Teddy Towne. The title comes from one of many actual female character breakdowns Borstein reads from to illustrate sexism in the industry.
Alex Borstein