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Moore took her professional name from her first husband, musician Freddy Moore, and is the mother of three daughters from her marriage to actor Bruce Willis. She has been married to actor Ashton Kutcher since 2005.

Moore was born Demi Gene Guynes in Roswell, New Mexico. As a child, she had a difficult and unstable home life. Her biological father, Charles Harmon, left her mother, Virginia King (November 27, 1943 – July 2, 1998), after a two-month marriage, before Moore was born. As a result, Moore had the surname of her stepfather, Danny Guynes (March 9, 1943 – October 1980 by suicide), on her birth certificate. Danny Guynes frequently changed jobs; as a result, the family moved a total of forty times. Moore has two younger half-brothers: James Craig Harmon (paternal) and Morgan Guynes (maternal, born 1967). Her parents were alcoholics who often fought and beat each other. Moore was cross-eyed as a child and wore an eye patch in an attempt to correct the problem until it was ultimately corrected by two surgeries. She also suffered from kidney dysfunction.

Moore's family settled in Los Angeles in 1976. She attended Fairfax High School in Hollywood, where her schoolmates included Red Hot Chili Peppers frontman Anthony Kiedis, bassist Michael Balzary (aka Flea) and actor Timothy Hutton. When Moore was 16, her friend Nastassja Kinski persuaded her to drop out of school to become an actress.

After training with John Casablancas, the founder of Elite Model Management, Moore made her film debut in the 1982 3-D science fiction/horror film, Parasite, which was a hit on the drive-in circuit, ultimately grossing $7 million. However, Moore was not widely known until she played the part of Jackie Templeton on the ABC soap opera, General Hospital, from 1982 to 1983. Moore also had an uncredited cameo at the end of the 1982 spoof Young Doctors in Love.

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In the mid-1980s, Moore appeared in the youth-oriented films St. Elmo's Fire, Blame It on Rio and About Last Night..., and she was often listed as one of the Brat Pack, a name the media dubbed a certain group of top young actors at the time. In 1988, she starred in The Seventh Sign directed by Carl Schultz. After the commercial success of Ghost, Moore was given more prominent roles in A Few Good Men, Indecent Proposal, Disclosure, and The Hunchback of Notre Dame for which she was the first actress to reach the $10 million salary mark.

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During the early 1990s, she was the highest paid actress in Hollywood. She never surpassed the success of Ghost, and had a string of less successful films like The Scarlet Letter, The Juror, Striptease, and G.I. Jane. Moore's Passion of Mind co-star Joss Ackland lambasted her by describing her as being "not very bright or talented", although he worked with her again on Flawless in 2008. At the same time, she produced and starred in a TV mini-series called If These Walls Could Talk, written by Nancy Savoca. A three-part series on abortion, Savoca directed two segments, including the one in which Moore played a single woman in the 1950s seeking a back-alley abortion. She was nominated for a Golden Globe for Best Actress for that role.
Moore was a founding "celebrity investor" in the Planet Hollywood chain of international theme restaurants (modeled after the Hard Rock Cafe and launched in New York on October 22, 1991) along with Sylvester Stallone, Arnold Schwarzenegger, and then-husband Bruce Willis.

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After a break from her acting career, Moore returned to the screen as the villain of the 2003 film Charlie's Angels: Full Throttle. In 2006, she appeared in Bobby which featured an all-star cast, including her husband Ashton Kutcher, although they did not appear in any scenes together. She later starred in the thriller film Mr. Brooks, which was released on June 1, 2007. She appeared in Jon Bon Jovi's longform video "Destination Anywhere" as Janie. In August 1991, Moore appeared nude on the cover of Vanity Fair under the title More Demi Moore. Annie Leibovitz shot the picture while Moore was seven months pregnant with her daughter Scout LaRue, intending to portray "anti-Hollywood, anti-glitz" attitude. The cover sparked an intense controversy for Vanity Fair and Moore. It was widely discussed on television, radio, and in newspaper articles. The frankness of Leibovitz's portrayal of a pregnant sex symbol led to divided opinions, ranging from complaints of sexual objectification to celebrations of the photograph as a symbol of empowerment. The photograph was subject to numerous parodies, including the Spy magazine version, which placed Moore's then husband Bruce Willis' head on her body. In Leibovitz v. Paramount Pictures Corp., Leibovitz sued over one parody featuring Leslie Nielsen, made to promote the 1994 film Naked Gun 33⅓: The Final Insult. In the parody, the model's body was attached to what is described as "the guilty and smirking face" of Nielsen. The teaser said "Due this March". The case was dismissed in 1996 because the parody relied "for its comic effect on the contrast between the original". In November 2009, the Moroccan magazine Femmes du Maroc emulated the infamous pose with Moroccan news reporter Nadia Larguet, causing controversy in the majority Muslim nation. In August 1992, Moore would again appear nude on the cover of Vanity Fair, modeling for the world's leading body painting artist, Joanne Gair in Demi's Birthday Suit. The painting is widely considered to be the best-known example of modern body painting artwork.