 The abuses perpetrated as part of the infamous Tuskegee syphilis study were made public in 1972, 40 years after the study was initiated. The resulting outcry led to the formation of the U.S. National Commission, which was charged with evaluating the ethics of clinical research with humans and developing recommendations for appropriate safeguards. These deliberations resulted in a series of recommendations for the conduct of clinical research, which became the framework for existing U.S. regulations. The U.S. regulations, like many regulations, place no clear limits on the risks to which competent and consenting adults may be exposed. In contrast, strict limits are placed on the level of research risks to which those unable to consent may be exposed, particularly children. In the case of pediatric research, the standard process for review and approval is limited to studies that offer a ‘prospect of direct’ benefit and research that poses minimal risk or a minor increase over minimal risk. Studies that cannot be approved in one of these categories must be reviewed by an expert panel and approved by a high government official. While this 4th category offers important flexibility, it implies that, at least in principle, U.S. regulations do not mandate a ceiling on the risks to which pediatric research participants may be exposed for the benefit of others. This reinforces the importance of considering how we might justify exposing participants to research risks, both minimal and greater than minimal, for the benefit of others.