Two sisters, Kellie and Lannie, see their single mother killed by her boyfriend after an argument when they are 13 and 14 years old. They are sent to live with an uncle (their mother's brother), and soon detest his wife since she gives preferential treatment to her son and resents their being in her home. Violence is the only way the two sisters know how to handle problems, so they kill the aunt. Their uncle promptly takes them out of his home because he fears for his son's safety. The two sisters are placed in a sanitarium and diagnosed with bipolar 1 disorder, which is a form of manic depression.
After five years, the two sisters are now 18 and 19 years old and released from the sanitarium because "they are better," see their uncle has sold the home they lived in, and go to college (California University). At the university classmates like Kellie, but have difficulty with Lannie. Since Lannie and Kellie are very close, Lannie becomes jealous of Kellie's being able to make friends.

Jeri D. Arnold assisted Terri Dawn Arnold with casting. However, before having auditions Terri Dawn cast Celeste Yarnall ("Star Trek"), Ron Millkie (FRIDAY THE 13TH), and Brinke Stevens (HAUNTING FEAR). Ola Murchison, who plays the university football coach, is a real-life retired NFL player. He played football for the Dallas Cowboys and the San Francisco 49ers. THE TWO SISTERS was shot in 18 days during the summer of 2006.