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The daughter of actors John Aniston and Nancy Dow, she began working as an actress at an early age with an uncredited role in the 1988 film Mac and Me. Her first major film role came in the 1993 horror comedy Leprechaun. She rose to international fame as Rachel Green on the television sitcom Friends from 1994 to 2004, for which she received the Primetime Emmy Award for Outstanding Lead Actress in a Comedy Series.

Aniston has since starred in several successful comedy films that have cumulatively grossed over $1.6 billion worldwide. These films include Office Space (1999), Bruce Almighty (2003), The Break-Up (2006), Marley & Me (2008), Just Go with It (2011), Horrible Bosses (2011), We're the Millers (2013), Dumplin' (2018), and Murder Mystery (2019). Aniston also starred in the acclaimed independent films The Good Girl (2002), Friends with Money (2006), and Cake (2014). In 2019, she returned to television, producing and starring in the Apple TV+ drama series The Morning Show, for which she received a Screen Actors Guild Award.

Aniston has appeared on many magazines' lists of the world's most beautiful women. Her net worth is estimated at US$300 million. She has a star on the Hollywood Walk of Fame. She is the co-founder of the production company Echo Films, established in 2008.