Mental illness continues to fuel the HIV epidemic. There is a high prevalence of mental disorders in the HIV-infected population and a high prevalence of HIV infection in the mentally ill. Without effective treatment of mental disorders, HIV treatment outcome is poor, and transmission of disease continues. High frequencies of mental illness are found in corrections facilities, among the homeless, among injection drug users, and in patients attending sexually transmitted disease clinics. Such populations must be targeted for effective mental health treatment if overall outcomes of HIV treatment are to be improved and transmission of HIV is to be reduced. This article summarizes a presentation on mental illness and the HIV epidemic made by Andrew F. Angelino, MD, at the 10th Annual Ryan White HIV/AIDS Program Clinical Update in June 2007.