Born in the Soviet Union, Spektor began studying classical piano when she was six. Her family emigrated in 1989, landing in New York City, where she continued her classical training. Spektor eventually studied composition at the Conservatory of Music at SUNY Purchase where she graduated with honors. She began writing pop songs in her late teens and made her recorded debut in 2001 with the self-released 11:11, a collection of songs heavily influenced by jazz and blues. Songs followed in 2002 and Soviet Kitsch in 2004.
Spektor’s commercial breakthrough came in 2006 on her fourth LP, Begin to Hope. The gold-certified album included the singles "Better," "Samson," “Fidelity,” which climbed the Billboard Hot 100 singles chart. Spektor’s fifth album, Far released in 2009, and sixth album, What We Saw From the Cheap Seats released in 2012, both debuted at No. 3 on the Billboard 200 albums chart. Regina's newest record, Remember Us To Life, came out in September 2016.
Spektor’s songs have appeared in TV shows and movies including Orange Is The New Black, Grey’s Anatomy, Weeds, How I Met Your Mother, Veronica Mars, The Good Wife, (500) Days of Summer, In Bruges, and The Chronicles of Narnia: Prince Caspian, as well as many more. Spektor played for the Obamas and guests at the White House and performed as part of philanthropic campaigns for HIAS, Doctors Without Borders, Pediatric Cancer Research Foundation, Amnesty International, Planned Parenthood, and many other organizations.