This paper discusses detection, prevention of transmission, and treatment of human immunodeficiency virus (HIV) infection among persons with serious mental illness, and suggests ways public mental health systems can address these issues. Pertinent references from 1990 through 1998 MEDLINE searches were reviewed. Persons with severe mental illness are at greatly increased risk of HIV infection due to increased likelihood of high-risk sexual behaviors and injection drug use. Formidable barriers to detection and effective treatment of HIV in this population can be attributed to its unique characteristics, lack of knowledge among mental and physical health care providers, and fragmented mental and physical health care systems. In the last five years, more effective treatments for HIV have become available. Public mental health systems need to implement active prevention practices, educate health care providers about key treatment issues, and develop effective linkages between mental and physical health care providers and systems.