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Dottie Zicklin (of Dharma & Greg) and Julie Larson (of The Drew Carey Show) were creators and executive producers.

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.The same year, a leaked sex tape of Handler was being offered for sale.Along with her photo being added to the documentary and accompanying photo mosaic, she also shared a "Photo Story" with a message that inspires people to take chances in life.In early 2014, Handler released the book Uganda Be Kidding Me, which was number one on The New York Times Best Seller list for two weeks and in the middle of the year did the standup show Uganda Be Kidding Me: Live, which was then released on Netflix in October 2014.The event took place at the Nokia Theatre in Los Angeles on September 12, 2010. After more than 1,000 episodes, the final episode of Chelsea Lately aired on August 26, 2014.

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 also signed a three-book deal with the imprint, the first of which is called Lies That Chelsea Handler Told Me, where her coworkers and family members discuss their experiences with Handler, which was released in May 2011 and also hit the top of the bestseller list.

In July 2010, during a tour stop in Salt Lake City, Handler took part in the "I Am Equal" photo documentary project in memory of her mother, Rita, who died from complications of cancer.

On August 18, 2010, it was announced that Handler would be the host of the 2010 MTV Video Music Awards (VMAs).

The announcement was surprising to many, including MTV representatives, who claimed that the final decision was unexpected.

The well-roundedness of 60 Minutes but faster, quicker, cooler." Handler has written five books that have made the New York Times Best Seller List, four of which have reached number one.