Risk of human immunodeficiency virus (HIV) infection exacerbates the already difficult lives of 1.5 million homeless adolescents in the United States. Homeless youths engage in sexual and substance-abuse behaviors that place them at increased risk of contracting HIV, and they demonstrate other problem behaviors that reduce their coping responses. Model HIV prevention programs and interventions for HIV-positive youths, implemented for homeless adolescents, need to be disseminated on a national level. Social policies must recognize adolescents' rights to satisfaction of basic survival needs; comprehensively address the needs of dysfunctional, disenfranchised, and single-parent families; and provide continuity of care for adolescents to facilitate independent living. Special provisions must be made when designing programs for gay, sexually abused, and substance-abusing youths.