Dershowitz is known for taking on high-profile and often unpopular causes and clients. As of 2009, he had won 13 of the 15 murder and attempted murder cases he handled as a criminal appellate lawyer. Dershowitz has represented celebrity clients including Mike Tyson, Patty Hearst, Leona Helmsley, Julian Assange, and Jim Bakker. Major legal victories have included two successful appeals that overturned convictions, first for Harry Reems in 1976, followed by Claus von Bülow in 1984 who had been convicted for the attempted murder of his wife, Sunny. In 1995, Dershowitz served as the appellate adviser on the O. J. Simpson murder trial, part of the legal "Dream Team", alongside Johnnie Cochran and F. Lee Bailey. Dershowitz was a member of the defense team for Harvey Weinstein in 2018 and for the first impeachment trial of President Donald Trump in 2020. He was a member of the legal defense team for Jeffrey Epstein and helped to negotiate a 2006 non-prosecution agreement on Epstein's behalf. He was later accused of rape by one of Epstein's underage victims in a sworn affidavit and in the Netflix documentary, "", which resulted in a lawsuit and his own counter lawsuit.