- Is right-handed but left eye dominant, evident when he is shooting his pistol on CSI: Miami (2002).
- Has had more success as a television actor than a movie actor. He was a popular cast member of NYPD Blue (1993), then quit that show to become a movie actor. After a series of unsuccessful movies, he joined the cast of CSI: Miami (2002), which shot him back into stardom.
- He once worked for a police department, standing in lineups for $25.
- His father is Italian, his mother is Irish.
- Has played the same character (Lt. Horatio Caine) on three different series: CSI: Crime Scene Investigation (2000), CSI: Miami (2002) and CSI: NY (2004).
- Son, Marquez Anthony, born September 15, 2005 (mother is girlfriend Liza Marquez).
- Daughter, Greta, born June 1, 1984, with Rachel Ticotin. She attended Yale University and is on the founding team of Good Eggs, a mission-driven company that aims to help grow and sustain local food systems worldwide.
- In the very first episode of the irreverent animated series South Park (1997) entitled "Cartman Gets an Anal Probe", Kyle urges his brother to jump from the open cargo-bay door of a hovering alien spaceship by saying, "Quick, Ike, do your impersonation of David Caruso's career," in reference to Caruso's then-lack of success after leaving NYPD Blue (1993). This scene was widely used in promos for the series.
- Was a co-owner of now-defunct Steam, an upscale clothing and home furnishings store in South Miami, Florida.
- Lives in Sherman Oaks, California and Miami Beach, Florida.
- Daughter, Paloma Raquel, born October 16, 2007 (mother is girlfriend Liza Marquez).
- In 1994, (according to court record) his ex-girlfriend, Paris Papiro, filed a palimony suit in which Caruso ended up paying an undisclosed sum in early 1995.
- He and his wife, Margaret Buckley, manage a classy clothing store in Miami, Florida. (March 2002)
- Attended and graduated from Archbishop Molloy High School in Briarwood, Queens, New York in 1974.
- A younger sister, Joyce Caruso, produces Fox News in New York.
- Worked as a movie theater usher while in high school.
- He hopes to buy a home on the French Riviera when he retires.
- After leaving NYPD Blue he had 2 major flops and periods of being out of work so he decided to quit Hollywood and move to Miami where he became a joint owner of a clothing and furniture store.
- He was originally scheduled to star in Metro (1997) alongside Eddie Murphy but dropped out of the film.
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