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Handler also made her interest in Benicio del Toro known, joked about Jeff Bezos and David Zaslav, and paid tribute to the late Michele and Rob Reiner.
No one was spared from Chelsea Handler at Sunday's Critics Choice Awards.
The comedian hosted the show for the fourth year in a row, opening up the ceremony with a monologue that pulled no punches from the star-studded crowd at the Barker Hangar in Santa Monica, California.
"You guys are all going to be spending the next three months together, so whoever wins tonight, get used to seeing them win," she cracked, as Sunday's ceremony was one of the first of this year's awards season, which culminates at the Academy Awards in March.
“You guys made amazing, original shows that everyone couldn't stop talking about -- until that gay hockey show from Canada came along," she added, addressing the TV nominees and the sudden popularity of Heated Rivalry. "Shoutout to Heated Rivalry; everyone loves it: Gay men love it, women love it, straight men who say they aren't gay but work out at Equinox love it!"
Following a joke about Sean Penn taking Cialis to prepare for his role in One Battle After Another, Handler turned her sights to his costar Benicio del Toro, urging him to "stop being so selective about what you do." She then added, "I need you in more movies, in more TV shows, in room 708 at the Andaz Hotel tonight," hitting on the actor.
Of their costar Leonardo DiCaprio, she quipped, "Leo almost didn't make it tonight because he was trapped on a boat in St. Bart's. It was just like the Titanic, but worse because Jeff Bezos was there."
She took aim at Warner Bros. Discovery CEO David Zaslav as well, while speaking about nominee Sinners.
"Sinners is the story of brothers who start this really fun place for entertainment and then vampires show up, suck the life out of everybody and burn it all to the ground. Fun fact, the original name of the main vampire was David Zaslav," she joked, before also pulling Nicki Minaj into her opening set.
"Sinners was a massive blockbuster. Although I haven't been invited into a Black person's house since, except Nicki Minaj's, but who wants to go over there?" she asked, following Minaj's support of Donald Trump and appearance at a Turning Point event with Erika Kirk.
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View StoryNoting the survivors in Sinners as KPop Demon Hunters used music to fight demons, she said, "the cast of KPop Demon Hunters is here. Not to be confused with Netflix's other music movie, '50 Cent: Diddy Hunter.'" 50 Cent, of course, is one of Handler's exes.
On a more serious note, Handler also took a moment to pay tribute to the late Rob Reiner, as well as his wife Michele, who were killed last month.
"Anyone who ever spent time with Rob Reiner knows that the minute that you met him, he felt like an old friend. When you were in a conversation with him, he was present, he was focused, and he was funny," she told the audience, "and he would ask you tons of questions. Whether you were discussing politics or film or the latest beauty trends, he was all in."
"After I sent him a text thanking him for dinner a few months ago," she continued, "he texted me back and said, 'We had so much fun with you last night. Thanks for explaining so much about plastic surgery. It was very edifying.'"
"Rob and Michele were tireless in their efforts to so many important causes, all stemming from one basic idea: decency, and that we should all look out for each other," she concluded. "I think we can all agree that we definitely need more of that. So, let’s use tonight as a reminder of that decency and as a reminder of everything Rob and Michele represented and fought so hard for."