Handler served as executive producer, along with Tom Werner (of That '70s Show), Mike Clements (of The Life & Times of Tim), and Tom Brunelle (of Chelsea Lately).In 2016, Handler filmed a documentary series for Netflix titled Chelsea Does, consisting of four episodes on marriage, Silicon Valley, racism, and drugs.In July 2007, Handler began starring on her own half-hour, late-night comedy series on E! The show proved to be a hit by averaging more than a half-million viewers since its premiere (much more than the average for a late night cable program) and having clips on You Tube with more than one million views. The show had a spinoff, the mockumentary After Lately, in which the various cast members, writers, crew, guests and even "hangers-on" of Chelsea Lately are shown bickering over trivial matters and competing for airtime on the show. Guest stars included: Reese Witherspoon, Jennifer Aniston, Jay Leno, Tori Spelling, Jenny Mc Carthy, Sharon Osbourne, Dave Grohl, Johnny Knoxville, and Jane Fonda.
She was also featured on the cover of Shape in April 2010, The Hollywood Reporter in June 2011, on Redbook On January 25, 2010, Handler confirmed, via her late-night talk show, that she had broken up with Harbert.
She hosted the late-night talk show Chelsea Lately on the E!
network from 2007 to 2014, and released a documentary series, Chelsea Does, on Netflix in January 2016. Other shows on which Handler has appeared include Weekends at the D.
L., The Bernie Mac Show, My Wife and Kids, and The Practice. and Scarborough Country, as well as a correspondent on The Tonight Show.
She hosted the first episode of the reality TV show On the Lot, but quit before the second episode aired, saying later that she left "because I smelled the disaster happening before it did." The show, produced by Steven Spielberg and Mark Burnett, was a competition for aspiring filmmakers vying for a chance at stardom. Handler was replaced by former Robin & Company entertainment anchor, Adrianna Costa.
She was a guest on Red Eye w/ Greg Gutfeld and The View, and she co-hosted The View on August 2, 2007, and September 5, 2008.