This article reviews the state of the science in HIV prevention for Hispanic adolescents. The article discusses the importance of preventing HIV in Hispanic adolescents. Literature is reviewed in three broad areas: (1) the prevalence rates of drug and alcohol misuse, sexual practices, and HIV infection; (2) risk and protective factors for drug and alcohol misuse and unprotected sex (in general and specifically for Hispanics); and (3) the state of HIV prevention intervention development and evaluation targeting Hispanic youth. Seven specific recommendations are advanced in areas that have the potential to further the field of HIV prevention for Hispanic adolescents.