There is a well-documented need for biomedical and behavioral research to improve treatment and care for adolescents living with or at risk for HIV. However, concerns exist about the legal and ethical issues surrounding adolescent HIV research, including concerns related to consent/assent and how best to balance autonomy and protection when conducting HIV-related research with minors. While minor participants are considered a vulnerable population, there also is recognition that adolescence is a time of emerging autonomy. Indeed, the requirement of parental or guardian permission may serve as an unnecessary barrier to adolescent HIV research, particularly for adolescents who possess adequate decisional capacity. The purpose of this article is to explore considerations related to, and to offer recommendations for, balancing autonomy and protection in the context of adolescent HIV research and to advance knowledge in the area of youth decisional capacity.