Born in the Virgin Islands and raised in New Jersey and Florida, Grammer was reared by his mother and maternal grandparents after his parents' divorce when he was a toddler. His beloved grandfather died when he was just 11 and the actor saw his father only twice before he was murdered on his front lawn when Grammer was 13. His father's killer was acquitted on the grounds he was insane at the time. Unfortunately, his father's demise would not be the only untimely death Grammer would have to survive. When he was 20, his younger sister was raped and murdered in Colorado Springs. He was expelled from The Juilliard School at this time after he stopped going to class because he was so heartbroken over his sister's murder. To make matters worse, his two half-brothers were killed in a scuba diving accident five years later.

In an attempt to deal with his personal demons, Grammer decided to fling himself into his work, performing with the Old Globe Theater in San Diego for three years in the late 1970s before returning to NYC where he made his daytime TV debut on the NBC soap "Another World". His big break came when he was cast as the psychiatrist fiance of Diane Chambers (Shelley Long) on the hit sitcom "Cheers".

The show's creators originally wanted John Lithgow for the brief, recurring role, but the actor was unavailable. Grammer's former Juilliard classmate Mandy Patinkin suggested Grammer to the New York casting director and he got the job, parlaying a six-episode stint into a career that would span nearly two decades essaying a shrink who outwardly seems adjusted, but is actually in desperate need of some intense psychotherapy himself. More than just another colorful barfly, Frasier was a character ripe with comic possibilities and stayed around long after Diane departed the premises. Grammer became a regular face (and occasionally just a voice) on TV once he began frequenting that beloved Boston watering hole, doing guest shots on many series including "Roc", "Star Trek: The Next Generation" and, most memorably, a recurring role on "The Simpsons" as Sideshow Bob, the underappreciated sidekick of Krusty the Clown with homicidal urges toward Bart Simpson. When the last call was finally sounded at "Cheers" in 1993, Grammer's character was the natural choice for a spin-off and "Frasier" went on to become a ratings winner and the only sitcom to win five consecutive Best Comedy Series Emmy Awards.

Grammer made his feature debut in the forgettable road comedy "Galaxies Are Colliding" (1992). With his renewed TV success, he leapt to the big screen with the lead in the comedy "Down Periscope" (1996), about a misfit Naval crew who must use a broken-down submarine for war exercises. Grammer has also voiced characters in the Mickey Mouse short "Runaway Brain" (1995), the feature length musical "Anastasia" (1997), the TNT animated version of "Animal Farm" (1999), his self-produced Spike TV! series "Gary the Rat" (2003), the big-screen spin-off of the animated TV series "Teacher's Pet" (2004) and, particularly memorably, as the narrator of the 1998 holiday-themed "How the Finch Stole Christmas" episode of the sit-com "Just Shoot Me."

He returned to the stage in 1999, to play the title character in "Sweeney Todd" opposite long-time friend Christine Baranski in L.A.'s Reprise! musical revival series. Earlier that year, Grammer had invited Baranski to appear on "Frasier" and both collaboration won kudos from critics and audiences alike. 2000 saw Grammer in a less successful stage endeavor as he attempted to fulfill a life-long dream by playing "Macbeth" on Broadway, having briefly portrayed the Bloody Thane once before (unsuccessfully, he felt) when he was still a green 25-year-old actor. The new production, which co-starred his Juilliard classmate Diane Venora, suffered scathing reviews, however, and closed after just 13 regular performances and eight previews. Grammer was not in the critical doghouse for long, though. Just a month after "Macbeth" was shuttered, he was nominated for yet another Emmy for his work in his smash sitcom "Frasier"--the actor eventually accumlated four Emmy and two Golden Globe trophies. In addition to returning to his own show for the 2000-2001 season, he also executive produced the new UPN sitcom "Girlfriends" and a pilot for the NBC cop drama "County 187", which was written by James Ellroy ("L.A. Confidential") and had a small role in the big screen comedy thriller "15 Minutes", starring Robert De Niro. Thanks to a deal signed in the summer of 2001, Grammer would be the highest paid actor on television beginning in the fall of 2002, making $1.6 million per episode of "Frasier" (Ray Romano would eventually eclipse Grammer's salary).

Grammer continued to deliver crackerjack performances in a variety of fare, including the holiday telepic "Mr. St. Nick" (2002), as George Washington in the TV movie "Benedict Arnold: A Question of Honor" (2003) and in the ensemble indie comedy "The Big Empty" (2003). But it was still "Frasier" for which he was most beloved, and the series experience a long-needed spike upward in quality when it entered into its tenth and final season in 2003-2004--in fact, the cast and crew were having so much renewed fun, Grammer briefly tried to convince the network to keep the show running one more season before deciding to close up shop. Although the passing of its NBC brethern "Friends" that same year dominated the headlines, "Frasier's" departure stirred similar emotion among viewers, and just as the show aired its final episode, new broke that Grammer (who had played Frasier Crane for 20 years, one year less than the all-time TV record-holder James Arness as "Gunsmoke's" Matt Dillon) and NBC were in discussions about launching a series chronicling the next phase in the life of the fussy psychiatrist.