She is known for her television roles as Stephanie "Sam" Whitmore on the NBC daytime soap opera Generations (1989–1991), as Megan Lewis on the Fox primetime soap opera Melrose Place (1996–1999),[1] and as Lily van der Woodsen on The CW series Gossip Girl (2007–2012).

She also starred in the short-lived series The Great Defender as Frankie Collet (1995), and in Kindred: The Embraced as Caitlin Byrne (1996).

In 1996, Rutherford joined the cast of Fox primetime soap opera Melrose Place, as Megan Lewis.

In 2007, Rutherford began starring as Lily van der Woodsen in the CW series Gossip Girl.

In 2016, Rutherford was cast in the ABC thriller Quantico playing the recurring role of Laura Wyatt.

[7] From 2018 to 2019, Rutherford played the recurring role of Melissa Daniels in the CW reboot series Dynasty.

In August 2009, Rutherford and Giersch reached a temporary settlement of joint physical custody, in effect until April 2010.

[20] In August 2012, in a widely reported decision,[18] a California Superior Court judge ruled that the 50/50 custody arrangement should remain and that, because Giersch is unable to travel to the United States, the children should live in France with him and attend school there, with Rutherford traveling there to visit them.

[21] In May 2015, Rutherford was granted temporary sole custody of her children, following a ruling that both her son and daughter be brought back to the United States from Monaco, where they had been living with their father since 2012.