Adults with severe mental illness (SMI) have been disproportionately affected by the HIV/AIDS epidemic. This systematic review of the empirical literature on SMI documents the prevalence and correlates of HIV risk behaviors, discusses clinical implications for HIV prevention, and recommends directions for future research. Prevalence rates of HIV risk behaviors were estimated using weighted means, and findings on correlates were synthesized. Across reviewed studies (N=52), the majority of adults with SMI were sexually active, and many engaged in risk behaviors associated with HIV transmission (e.g., unprotected intercourse, multiple partners, injection drug use). HIV risk behaviors were correlated with factors from the following domains: psychiatric illness, substance use, childhood abuse, cognitive-behavioral factors, and social relationships. A proposed model illustrates the multiple pathways linking these domains to HIV risk behavior. Further research using improved methodologies (e.g., longitudinal designs, standardized measures, multivariate analyses) is needed to examine the broader social context in which HIV risk behavior occurs and identify underlying processes. HIV prevention efforts targeting adults with SMI must occur on multiple levels (e.g., individual, group, community, structural/policy), address several domains of influence (e.g., psychiatric illness, trauma history, social relationships), and be integrated into existing services (e.g., psychotherapy, substance abuse treatment, housing programs).