Her paternal great-great grandparents were John Drew and Louisa Lane Drew. Her paternal grandparents were John Barrymore and Dolores Costello, whose father Maurice Costello was an actor. She is the great-niece of Lionel Barrymore, Ethel Barrymore, and Helene Costello, and the great grandniece of John Drew, Jr., actress Louisa Drew, and silent film actor/writer/director Sidney Drew. Her father John Drew Barrymore was an actor. Her half-brother John Blyth Barrymore is an actor. Her mother the Hungarian-American Jaid Barrymore has also acted.

Her first name Drew was the maiden name of her paternal great-grandmother, Georgiana Drew; her middle name Blyth was the original surname of the dynasty founded by her great-grandfather, Maurice Barrymore.

Her career began at the age 11 months when she auditioned for a dog food commercial. When she was bitten by her canine co-star, the producers feared she'd cry, but she merely laughed, and was hired for the job.

She shot to fame when she co-starred in the 1982 Steven Spielberg film E.T. the Extra-Terrestrial. At the age of 7, on November 20, 1982, Barrymore became the youngest-ever guest host of Saturday Night Live. She performed in a skit where she revealed that she killed E.T. She also received a Golden Globe nomination for Best Supporting Actress in 1984 for her role in Irreconcilable Differences.

In the wake of this sudden stardom, she endured a notoriously troubled childhood, drinking alcohol by the time she was 9, smoking marijuana at 10, and snorting cocaine at 12. Barrymore later described this period of her life in her 1990 autobiography, Little Girl Lost.

Though overcoming her substance abuse problems by the time she entered adulthood, she maintained her "bad girl" image, and leveraged her new-found role as a sex symbol to stage a career comeback playing a teenage seductress in Poison Ivy, and posing nude for the January 1995 issue of Playboy.

Steven Spielberg gave her a quilt for her 20th birthday with a note that read "Cover yourself up." Enclosed was a copy of her Playboy appearance, with the pictures altered by his art department so that she appeared fully clothed.

At that time she had also appeared nude in her last five movies. During a 1995 appearance on The Late Show with David Letterman, Barrymore shocked the normally unflappable host by climbing onto his desk and flashing him (but with her back to the camera) for his birthday. She also modelled in a series of Guess? jeans ads during this time.

Barrymore has continued to be highly bankable. She is especially adept at romantic comedies: The Wedding Singer and 50 First Dates. She has also produced several films, including Charlie's Angels. Maxim magazine featured Barrymore and her fellow Angels in their Girls of Maxim gallery.

She has also recently explored more dramatic roles in movies such as Riding in Cars with Boys, where she played a teenage mother in a failed marriage with the drug-addicted father (based on the real-life story of Beverly D'Onofrio), Confessions of a Dangerous Mind, and Donnie Darko.

Barrymore's career makes for colorful copy. In the words of Yahoo! Movies:

Heir to a Hollywood dynasty, child star, prepubescent drug and alcohol abuser, teenage sexpot, and resurrected vessel of celluloid purity, Drew Barrymore is nothing if not the embodiment of the rise and fall of Hollywood fortunes, self-reinvention, and the healing powers of good PR.

She was the subject of My Date with Drew (2005). In it, an aspiring filmmaker and fan uses his limited resources in an attempt to gain a date with her.

On February 3, 2004, she received a star on the Hollywood Walk of Fame.

Barrymore was married to Welsh bartender turned bar owner, Jeremy Thomas, from March 20 to April 28, 1994, and to comedian Tom Green from July 7, 2001 to October 15, 2002 (Green filed for divorce in December 2001). She is currently dating drummer Fabrizio Moretti of The Strokes.

For more details on this topic, see Tom Green#Marriage to Drew Barrymore.