This article reviews four areas of pediatric research in which we have identified questionable levels of allowable risk, exceeding those foreseen by the Commission. They are the following: (1) the categorization of increasingly risky interventions as minimal risk in a variety of protocols; (2) the increasing number of applications for federal panel review of research not otherwise approvable because of higher projected risk levels; (3) research on asymptomatic at risk children; and (4) the inclusion of children and adolescents in placebo-controlled trials for participants of all ages without performing subgroup analysis. While embracing the imperative to include children in research is an encouraging step towards providing the pediatric population with effective medical care and finally eradicating the therapeutic orphan, we must ensure that this research does not become overly permissive.