AbstractThe prevention and treatment of HIV infection are particularly difficult in certain subpopulations unless consideration is given to their unique characteristics. These characteristics and the strategies to address them are considered with respect to adolescents, rural/low-incidence populations, gay and bisexual men, African-Americans, Latinos, women, and the mentally ill. Alcohol and other drug use must always be addressed in treatment and prevention efforts even if patients do not meet the full criteria for chemical dependence. Health care providers need to consider their own biases as well as the overt and covert messages they project in order to provide the best possible care to these subpopulations.