Gay and bisexual male adolescents and young adults in the United States have been disproportionately impacted by the HIV pandemic. Despite the steadily increasing rise in their HIV infection rates, there has not been a commensurate increase in HIV prevention programs targeted to the unique social and sexual lives of these youths. Programs that address cultural and contextual factors that influence sexual risk and protective behaviors need to be developed, implemented, and rigorously evaluated. These interventions should address the potential influences of sexual and gay culture on the HIV risk/protective behaviors of gay and bisexual adolescents, as well as the influence of more traditional cultural factors related to ethnicity. The influence of contextual developmental factors should also be addressed. This may include an incorporation into prevention programs of the societal-level influences of heterosexism and masculinity ideology and the individual-level influences of sexual identity and ethnic identity development. Researchers and interventionists need to be creative and innovative in their HIV prevention approaches and ensure that programs are grounded in the lives and realities of gay and bisexual adolescents and young adults.