Jillian has been acting since 1961 when she played "Little Bo Peep" in the Disney film, Babes In Toyland. She appeared in the Rosalind Russell- Natalie Wood 1962 movie version of Gypsy. She later became a regular on the 1960s sitcom Hazel and did voice acting for Scooby Doo and Sealab 2020 in the early 1970s.

She is best known for her early 1980s TV series, It's a Living, a sitcom that elevated Jillian to sex symbol status. She was last signed into this series and received last place billing. During her time on the series, she portrayed Mae West in a made-for-TV film, and quit It's a Living for a couple of years, later returning with top billing after it had been renamed Making a Living.

Jillian appeared in more than 25 films, mostly for TV. She also starred in two short-lived sitcoms, an early 1980s effort entitled Jennifer Slept Here in which she played a ghost in a variation of The Ghost and Mrs. Muir and a 1989 series entitled, simply, Ann Jillian.

Jillian married Andy Murcia, a Chicago police sergeant, in 1977 and shortly after Murcia retired to manage his wife's career. In the mid-1980s, the then 35-year-old actress made headlines when she was diagnosed with breast cancer and she became a vocal advocate for cancer research and prevention. Her own cancer was beaten following a double mastectomy and her battle with the disease was chronicled in the top-rated 1988 made-for-TV film, The Ann Jillian Story in which Jillian portrayed herself.

Jillian has continued to act and had a son in 1992. Her TV and film credits have been sporadic since the late 1990s, as she decided to devote herself to raising her son Andrew Joseph and to promoting breast cancer issues. Today, she mostly works as a motivational speaker and also performs as a singer in corporate and symphony pops circles. Ann, husband and son reside in the San Fernando Valley area of Los Angeles.