In the mid-1990s that Joosten made the move to Hollywood, where she took guest roles in television series such as Roseanne, Home Improvement, Picket Fences, Murphy Brown, ER, Seinfeld, Frasier, Just Shoot Me!, Buffy the Vampire Slayer, Dharma & Greg, Las Vegas and The Drew Carey Show. In the 1997 episode of Frasier, 'Roz's Turn', Joosten appeared as Vera, the mother and personal secretary of Frasier's conniving agent, Bebe Glazer, played by Harriet Sansom Harris. The pair would later be reunited to play opposite neighbors in Desperate Housewives.
In 1999, Joosten took the role for which she is best-known, as Delores Landingham, secretary to President of the United States Josiah Bartlet (played by Martin Sheen) in The West Wing. Joosten played the role for two seasons, until her character's death in a car crash in 2001. She would return to the show twice more in flashback episodes.
Joosten's role on The West Wing gave her an entrance into more significant guest roles on notable television series. Since 2001, she appeared on TV in such shows as Scrubs (appearing in "My Old Lady", which won a Humanitas Prize as well as reappearing in two later episodes), My Name is Earl, Spin City, The X-Files, Judging Amy, Monk, Charmed, Will & Grace, Malcolm in the Middle, Grey's Anatomy, The Suite Life of Zack and Cody, Reba, So Little Time, Gilmore Girls, The Closer and a recurring role as one of the less intimidating incarnations of God seen by the title character (played by Amber Tamblyn) on the TV series Joan of Arcadia.
In 2005, Joosten appeared in the film Wedding Crashers, starring Vince Vaughn and Owen Wilson. Joosten also had a recurring role on Desperate Housewives as Karen McCluskey. For this role, Joosten won two Emmy Awards for Outstanding Guest Actress in a Comedy Series in 2005 and 2008 and once again got nominated for 2010, and appeared as a presenter at the 2005 and 2008 Emmy Awards telecasts. She also received Screen Actors Guild Award nominations with the rest of the cast for Outstanding Performance by an Ensemble in a Comedy Series from 2006-2008. She was promoted to a member of the regular cast in Season 6. However, the Emmys still billed her as a "Guest Actress" when she was nominated for a third time for Outstanding Guest Actress in a Comedy Series for the 2010 Emmys. She then played In Aunt Jackie in Alvin and the Chipmunks: The Squeakquel in 2009.
In 2005 and 2008, Joosten won an Emmy for Outstanding Guest Actress - Comedy Series for her portrayal of Karen McCluskey in Desperate Housewives.
In 2007, in an appearance on The View, she revealed that she was a lung cancer survivor, after many years of smoking (which she subsequently quit), and gave some tricks for trying to beat the habit of smoking. Coincidentally, her guest roles on My Name is Earl and Grey's Anatomy revolved largely around her character attempting to quit smoking.
In 2001, she quit her 45 year smoking habit when she was diagnosed with lung cancer. In September 2009, Joosten was diagnosed with lung cancer for a second time. She subsequently underwent surgery and four rounds of chemotherapy, and was officially declared cancer-free in January 2010.
Right after the Desperate Housewives finale aired, Joosten was featured in a PSA for lung cancer.
To Quote Kathryn Joosten, "I smoked because Betty Davis said it was very glamorous. I smoked because it was seen everywhere and done everywhere. I got addicted because the tobacco companies add additives to their tobacco to make it more addictive. I'm damned mad at all of them".
Good Night Ms. Joosten