Siff is an alumna of The Bronx High School of Science[2] and of Bryn Mawr College,[3] where she majored in English and graduated in 1996.

[4][5][6] Shortly after graduating, Siff also worked as a temp at a hedge fund, an experience she drew on for her role in Billions.

[citation needed] She also appeared in a small role as a burn victim on Nip/Tuck during that time, before being cast as Dr. Tara Knowles on Sons of Anarchy in 2008.

She has appeared in such films as Then She Found Me (2007) as Lily, Push as a psychic surgeon (called a Stitch) named Teresa Stowe, sent to help Nick (played by Chris Evans), Funny People (2009) as Rachel, Leaves of Grass (2010) as Rabbi Renannah Zimmerman, and Concussion (2013) as Sam Bennet.

In 2020, Siff provided the voice for the titular subject of "Polly Platt: The Invisible Woman", over the course of a season of Karina Longworth’s film history podcast You Must Remember This.