She played the female lead in the independent sports drama The Final Season.
She has appeared in numerous episodes of the Seth Green comedies Titan Maximum and Robot Chicken.
In 2011, she was selected by the Obama administration as a Champion of Change for Arts Education.
In 2017, Rachael Leigh Cook reprised her "This Is Your Brain on Drugs" role twenty years later for a PSA by the Drug Policy Alliance critiquing the War on Drugs and its contribution to mass incarceration, structural racism and poverty.
The ad was posted to You Tube on April 20, 2017 in recognition of 4/20.
To hone his acting skills, he went to the Unitec School of Performing Arts.
Cook's latest voice-over role is for the video game Yakuza in which she voices the role of Reina.
Cook first gained national attention in 1997, when she was featured in the famous This Is Your Brain on Drugs PSA television advertisement, in which she proceeds to destroy a kitchen with a frying pan as she lists the important things in life that heroin harms.
In 2008, she guest-starred in an episode of the USA Network series Psych as Abigail Lytar. In February 2010, Cook signed on to play the female lead role in Fox TV's comedy pilot Nirvana.
In 2012, Cook signed on to play the female lead role in the TNT crime drama series Perception opposite Eric Mc Cormack.Cook began auditioning for acting work at the age of 14.