Treatment research on adolescent substance use disorders raises a number of important ethical and legal concerns which have not been widely acknowledged. This paper explores these concerns as they relate to fundamental ethical principles in the conduct of human research. The issues discussed include tensions between conflicting regulations governing informed consent for research and treatment of adolescents, the capacity of adolescents to give informed consent, potentially coercive elements related to research on substance use treatment, problems associated with confidentiality and release of information, research vulnerability associated with substance use, and ethical implications of distinctions between effectiveness and efficacy research. Suggestions for ways investigators may address these concerns are provided.