Lowe began to regain some ground with an hilarious appearance on NBC's "Saturday Night Live" (during which Dana Carvey's Church Lady paddled him for his indiscretions) and a villainous turn in Curtis Hanson's "Bad Influence" (1990). He made his Broadway debut as a virginal philosophy student in the National Actors Theatre staging of Feydeau's "A Little Hotel on the Side" in 1992. His screen roles improved, allowing him to be appropriately sleazy as a TV mogul in "Wayne's World" (1992) and to hold his own against the powerhouse acting of Natasha Richardson and Maggie Smith in the small screen remake of "Suddenly Last Summer" (PBS, 1993). For his portrayal of a deaf mute in the ABC miniseries "Stephen King's The Stand" (1994), Lowe received some of his best reviews. He temporarily shifted to work behind the scenes, producing and co-starring (with Bill Paxton) in the Western "Frank and Jesse" (HBO, 1995) and directing and scripting the short "Desert's Edge" (Showtime, 1997).

Not forsaking acting, he delivered a solid supporting turn as a right-wing Christian leader in "Contact" (1997) and gave an impressive comedic performance and showcased his strong Robert Wagner impersonation with a co-starring role as Young Number Two in "Austin Powers: The Spy Who Shagged Me". With a failed sitcom pilot under his belt, and a successful starring role in the 1999 NBC action TV-movie "Atomic Train",

Lowe returned to series television for the first time since 1979 with a regular role on the NBC drama "The West Wing". He was featured in the ensemble of this White House set series as lothario Sam Seaborn, deputy communications director for the US President (Martin Sheen), a role that made the most of the former pretty boy's newly distinguished good looks, while at the same time exhibiting his magnetic presence and notable talent. In 2001, he earned an Emmy nomination for his work on the series, but in 2002 decided to leave "The West Wing" becuase the show producers would not agree to a pay increase. Despite some reported wrangling on behalf of his co-stars--most prominently Martin Sheen--to keep Lowe on the hit series, the actor was written out of the series, and his exit in Feb. 2003 was executed even earlier than expected . In early 2003, Lowe was tapped to star in a new NBC drama, the legal ensemble "Lyon's Den," in which he played an idealistic attorney trying to escape the shadow of his father, a U.S. Senator.