"I've made great friends, a lot of enemies, and I have personally lost and gained 3,500 pounds."
The guest-star-jammed finale included cameos from a galaxy of stars, like Ellen DeGeneres, who demanded to know why she was never invited to be on the show – see below.
Other guests for the evening included Sandra Bullock, Jennifer Aniston and Handler's ex 50 Cent. Miley Cyrus was on hand to perform as well, though the evening's biggest musical moment was saved for last.
Dozens of stars, including Gwen Stefani, Alanis Morissette, Gerard Butler, Kevin Nealon, Dave Grohl and Tim Allen, joined Handler for a musical number called "Goodbye to E!."
"It's time to move on," they sang. "[Handler] wants to sing. She wants to dance and get her groove on."
Handler's groove will be next gotten on Netflix (a move she couldn't resist plugging at the end of her finale, yelling, "I'll see you on Netflix!" to the audience), with a stand-up special set to air next month. She's also been confirmed to host the streaming service's first talk show, though a date has not been set.