[2][3] She has regularly appeared on shows such as A Prairie Home Companion, Mountain Stage, and contributed vocals to the Grammy-winning album True Life Blues: The Songs of Bill Monroe.

[1] She is known for her interpretations of classic songs by artists such as Tom Waits, Memphis Minnie, Willie Dixon, Chuck Berry, Si Kahn, Terence Trent D'Arby, and Kate MacLeod.

Her family was immersed in music,[1] and her mother frequently drove Mollie and her younger brother Tim to local performances [4] by 1960s[1] musicians such as The Beatles, Wheeling Symphony, Count Basie, Dave Brubeck and Ray Charles.

[1] In high school, she and her brother Tim began playing Peter, Paul, and Mary songs as a duo at church and local coffeehouses.

"[6] In 1976, her brother and close friend Tim was still living in Colorado as a bluegrass and folk musician, and playing in the Ophelia Swing Band.

[6][7] She eventually accepted Tim's invitation to move there,[4] and began singing and earning a living in local Denver and Boulder bars on the R&B and jazz club circuits.

[8] The album received positive reviews, with the Graham Weekly quoting "The album ranges from very traditional material to contemporary songs, from gospel to jazzy to Western Swing, and even includes a wonderful acoustic treatment of a Terence Trent D'Arby pop song...virtually every one of the dozen tracks is a gem with either Ms. O'Brien's vocal shining or the musical arrangements being brilliant, or both.

[8] The album included a variety of classic and newer Americana and rock songs by artists like Memphis Minnie, Willie Dixon, and Chuck Berry.

Rolling Stone positively reviewed the album, and said "she steers clear of corn in stories about gambling men, love, loss and sexual politics in the rustic South.

"[8] The Washington Post also gave the album a glowing review for her reinterpretation of Americana pop singers like Randy Newman, John Hiatt, and Steve Goodman, quoting "The precision of her phrasing, the smooth flow of her delivery and the sheer beauty of her alto make her one of the best interpretive singers in American pop today.

Rhythms in Australia wrote "She has the chameleon-like ability to interpret blues, country, folk, jazz, pop and gospel and has the capacity to make other people's songs sound like they were written especially for her.

[1] She has sung numerous times on A Prairie Home Companion, including as a part of the Hopeful Gospel Quartet and host Garrison Keillor.

[11] Also released by Remington,[1] it features classic American blues, gospel, folk[6] and show tunes by artists such as Tom Waits, Jesse Winchester, Harry Nilsson, Richard Thompson and George Harrison.