A biopsychosocial perspective is employed to assess associations among situational and psychosocial variables related to health, health care, and HIV/AIDS risk behaviors among 479 homeless men (aged 18-64 years). Poor health was not significantly associated with sexual risk behaviors and was only modestly associated with injection drug use (IDU). Health care was not significantly associated with sexual risk behavior or IDU. HIV/AIDS risk behaviors were highly associated with homelessness severity and posttraumatic stress disorder. IDU was significantly associated with greater emotional distress and was more likely among younger men and among White men. Sexual risk behavior was more frequent among those who had particularly poor-quality housing such as living on the street or in abandoned buildings. Because interactions with the medical community are limited and not associated with HIV/AIDS risk, outreach in areas in which homeless men congregate, mental health and substance abuse treatment, and permanent supportive housing may help reduce HIV risk among homeless men more effectively. © 2009 Sage Publications.