With more than half of new infections occurring among youth, HIV/AIDS remains a major contributor to morbidity and mortality in Uganda. Semi-structured interviews were performed with 48 adolescents and 15 adult key informants in a rural Ugandan community to identify influences on adolescent sexual decision-making. Inductive data analytic methods revealed five thematic influences: (1) social pressure, (2) decline of the Senga (a familial figure who traditionally taught female adolescents about how to run a household), (3) cultural barriers to condom use, (4) knowledge of HIV transmission and modes of prevention, and (5) a moral injunction against sex before marriage. Influences were classified as HIV/AIDS risk and protective factors and organized to form an explanatory framework of adolescent sexual risk-taking. Risk factors pull youth toward risky behavior, while protective factors push them away. Predominance of risk over protective influences explains persistent sexual risk-taking by Ugandan youth. HIV prevention programs designed for Ugandan adolescents should take competing factors and sociocultural and economic influences into account.