In 2005 Lowe starred in the miniseries Beach Girls on the Lifetime network, based on the Luanne Rice novel of the same name.
The series premiere received the highest ratings for a movie premiere in Lifetime history.
In January 2007, ABC announced that Lowe would be staying on Brothers and Sisters as a "special guest star" for the rest of Season 1 after Lowe's initial appearance on the show in November 2006 brought the best ratings and demographic showing for the show since its premiere.
Despite his two cancelled TV series and flops like View From the Top and the made-for-TV movie Perfect Strangers during his post–West Wing run, Lowe found success in the TV miniseries genre.
That same year, Lowe filmed Stir of Echoes: The Homecoming, the sequel to the 1999 Kevin Bacon thriller Stir of Echoes.
In 2006, it was announced that Lowe would join the cast of Brothers & Sisters for a guest run of several episodes.
Lowe has also appeared in a televised advertisement for 'Visit California', along with other celebrities including Governor Arnold Schwarzenegger.
(In the advertisement campaign, he was usually pictured in a white tee-shirt printed with the California state flag.) Lowe had a supporting role in the 2009 movie The Invention of Lying In 2010, he appeared in the biography of the Brat Packers called: Brat Pack: Where Are They Now?