Coinfection with HIV hastens the progression of liver disease in persons with hepatitis C virus (HCV) infection. As mortality directly due to HIV continues to decrease among persons who are HIV-positive, coinfection with HCV has emerged as a leading cause of death. There is increasing attention to the need to actively treat HCV infection in HIV/HCV coinfected patients. Current HCV treatment with pegylated interferon and ribavirin achieves sustained viral response in up to 40% of coinfected patients but has numerous neuropsychiatric side effects. Providers are hesitant to begin HCV treatment in the coinfected population given the high prevalence of existing psychiatric illness, cognitive impairment, and substance use disorders. There is an urgent need for research into the psychiatric and behavioral predictors of HCV treatment adherence and virologic outcome, as well as into the optimal psychiatric management of the neuropsychiatric sequelae of HCV therapy.