After he acquired a reputation as a skilled character actor in the 1980s and 1990s, Pastorelli's career went into decline after the death of his girlfriend under mysterious circumstances at his home in 1999.

He initially intended a career as a professional boxer, but had to abandon the sport due to injuries sustained in a near-fatal high-speed car crash at the age of 19 (he later claimed that he had a "near death" incident at this time, and that he had experienced himself looking down from above upon his body in the hospital bed with his father at the bedside overcome with grief).

His big break in television came with the role of the gruff but lovable house painter Eldin Bernecky on the series Murphy Brown, which was a ratings hit, and he stayed with the show for seven seasons from 1988 to 1994.

On the evening of March 15, 1999, during an incident at his Hollywood home, Pastorelli's 25-year-old girlfriend, Charemon Jonovich, was killed by a gunshot to the head.

[7] Pastorelli was exonerated of responsibility for Charemon Jonovich's death and received public expressions of sympathy within Hollywood and from the Los Angeles media, but his career went into noticeable decline afterwards.

He developed a friendship with Glenn Close towards the end of his career, and appeared alongside her in the television films The Ballad of Lucy Whipple, and in South Pacific in 2001.