Adolescents, despite their disproportionate burden of disease, often are excluded from sexually transmitted infection and HIV biomedical prevention clinical trials. The 3 principles of the Belmont Report (justice, respect for persons, and beneficence, U.S. Department of Health and Human Services, 1979) can inform our understanding of the ethical imperative to include minors in these trials. Investigators and institutional review boards need to have an understanding of what constitutes no more than minimal risk, that is, what is part of adolescent well-child care. Although cognitive development extends into the young adult years, evidence suggests that in most situations research decision-making capacity of an older minor is similar to that of a young adult. Depending on the specifics of the study, parental involvement may range from parental consent while protecting confidentiality to adolescent self-consent with a waiver of parental consent. Regardless of the level of parental involvement, protection of adolescents enrolled in trials will require strategies that guard against the risk of accidental loss of confidentiality. We outline a number of ways in which pediatric psychologists can assist clinical trial investigators and institutional review boards to ethically recruit and enroll minors into biomedical prevention trials. Furthermore, a pediatric psychologist can contribute to needed research on adolescent decision making and parental involvement to develop more sophisticated approaches to involving minors in HIV and sexually transmitted infection biomedical clinical trials.