He continued to appear in the series until the end of the 2009–10 season.
Unhappy with the stories and his lack of screen time in the fourth season, Lowe announced he would leave.
The year 2004 marked his return to this genre; he had appeared in 1994's The Stand, based on Stephen King's book of the same name.
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.
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.
In that same year, Lowe filmed his role as a movie agent in the 2006 independent film Thank You for Smoking.
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.
One of Lowe's earliest roles came in the 1983 TV film Thursday's Child, for which he received his first Golden Globe Award nomination for Best Supporting Actor in a Series, Miniseries, or Television Film.
His breakthrough role was his big screen debut in 1983, when he and Emilio Estevez were cast in Francis Ford Coppola's The Outsiders. Elmo's Fire, making them the two more prominent actors from the group known as the Brat Pack. followed, with Demi Moore (who had starred alongside Lowe in St. He then received his second Golden Globe Award nomination for Best Supporting Actor for his role as the mentally disabled Rory in Square Dance (1987).
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.