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Horner won two Academy Awards for his musical composition to James Cameron's Titanic (1997), which became the best-selling orchestral film soundtrack of all time. He also wrote the score for the highest-grossing film of all time, Cameron's Avatar (2009). Horner's other Oscar-nominated scores were for Aliens (1986), An American Tail (1986), Field of Dreams (1989), Apollo 13 (1995), Braveheart (1995), A Beautiful Mind (2001), and House of Sand and Fog (2003). Horner's other notable scores include Star Trek II: The Wrath of Khan (1982), Willow (1988), The Land Before Time (1988), Glory (1989), The Rocketeer (1991), Legends of the Fall (1994), Jumanji (1995), Casper (1995), Balto (1995), The Mask of Zorro (1998), Deep Impact (1998), The Perfect Storm (2000), How the Grinch Stole Christmas (2000), Troy (2004), The New World (2005), The Legend of Zorro (2005), Apocalypto (2006), The Karate Kid (2010), and The Amazing Spider-Man (2012).

Horner collaborated on multiple projects with directors including James Cameron, Don Bluth, Ron Howard, Joe Johnston, Edward Zwick, Walter Hill, Mel Gibson, Vadim Perelman, Jean-Jacques Annaud, Nicholas Meyer, Wolfgang Petersen, Martin Campbell, Phil Nibbelink, and Simon Wells; producers including Steven Spielberg, George Lucas, David Kirschner, Brian Grazer, Jon Landau, and Lawrence Gordon; and songwriters including Will Jennings, Barry Mann, and Cynthia Weil. Adding to his two Academy Awards wins, Horner also won six Grammy Awards, two Golden Globes, and was nominated for three BAFTA Awards.

Horner, who was an avid pilot, was killed in a single-fatality crash while flying his Short Tucano turboprop aircraft. He was 61 years old. The scores for his final three films, Southpaw (2015), The 33 (2015), and The Magnificent Seven (2016), were all completed and released posthumously.