(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?He also appeared on The Tonight Show with Conan O'Brien.
In 2006 he filmed The Perfect Day for TNT, in which he took a pay cut to film in New Orleans in order to help the hurricane-ravaged area.
That same year, Lowe filmed Stir of Echoes: The Homecoming, the sequel to the 1999 Kevin Bacon thriller Stir of Echoes.
In 2004 Lowe starred in the TNT remake of the Stephen King miniseries Salem's Lot which was the highest rated cable program of that summer and the highest ratings TNT original programming had at the time.
In 2005 Lowe starred in the miniseries Beach Girls on the Lifetime network, based on the Luanne Rice novel of the same name.
In June 2006, he was the guest host for an episode in the third series of The Friday Night Project for the United Kingdom's Channel 4.
Lowe has also appeared in a televised advertisement for 'Visit California', along with other celebrities including Governor Arnold Schwarzenegger.
But the acclaimed cast of the show—including Allison Janney, Richard Schiff, Dulé Hill, John Spencer, Bradley Whitford, Martin Sheen (whose President Bartlet was initially scripted as a small role) and Stockard Channing (whose First Lady was initially scripted as a guest role)— were all strong actors and eventually Lowe's character was no longer the lead.
Lowe and series creator Aaron Sorkin soon found themselves at odds over the network's meddling with the show, most notably the network demanding changes in the Sam Seaborn character.
He recalled meeting Paul Newman there, and that the older actor encouraged him to work in the theatre in 1993 when filming a British TV production of the Tennessee Williams play Suddenly, Last Summer with (the now) Dame Maggie Smith and Natasha Richardson.
and two Golden Globe Award nominations for Best Actor in a Drama Series.
The series premiere received the highest ratings for a movie premiere in Lifetime history.