Zedek grew up in the Washington, D.C. metropolitan area, attending Springbrook High School in Maryland, where she played clarinet in the marching band under band director Charles Sickafus. The early punk era of the late 1970s in which she came of age, and in particular Patti Smith, contributed deeply to the formation of her musical aesthetic. While still in high school she would travel with her brother, Dan Zedek (currently the editorial design director at the Boston Globe), to New York to see Smith perform.

Zedek moved to Boston in 1979, attending Boston University for one semester before deciding to pursue a musical career instead. Her first band, the all-female White Women, broke up after a couple years, and she formed the Dangerous Birds. This group had somewhat more success, including a single, "Smiling Face (Do you Recognize Me?)" that achieved airplay on college and alternative-commercial radio; but Zedek wanted a more "violent" sound in contrast to the somewhat "girlie pop" tendencies of her Dangerous Birds bandmates. Her next project, Uzi, worked to this aim, producing an EP "Sleep Asylum." The EP was characterized by elusive yet subtly menacing lyrics superimposed over lugubrious but driving instrumental tracks that featured layers of dense, murky yet muscular guitar arrangements blended with heady synthesizer and tape effects. But despite the promise of "Sleep Asylum", Uzi dissolved due to tension between Zedek and the band's drummer, Danny Lee.

She next took the role of primary vocalist for New York City's Live Skull, a band already well-established. While the album "Dusted," the first product of this collaboration, reflected an intense synergy between Zedek's vocal style and the complexly histrionic instrumental work of Live Skull, the followup "Positraction" floundered, and Live Skull also disbanded due to conflicts in 1990. By this time Zedek had also run into problems with regard to heroin addiction. Motivated to quit, she returned to Boston and the support of her friends. She soon cofounded Come, with former Codeine drummer Chris Brokaw. Here she had her biggest successes, releasing four albums before the group disbanded in 2001. That same year she also released Been Here And Gone, her first solo project. Zedek was also a participant in the 1998 Suffragette Sessions tour, organized by the Indigo Girls.

Despite limited commercial success, Zedek has been highly critically acclaimed throughout her career and has arguably been deeply influential within the indie-rock realm, particularly through her influence within the prolific Boston indie scene that has spawned so many noteworthy artists.