The ethical conduct of clinical research in children is challenged by the inherent vulnerability of this population. Children are both incompetent decision makers and have a right to custody (ie, protection), yet they must also be participants in research that will advance the care of pediatric disorders or they risk becoming "therapeutic ophans." Consensus guidelines exist for the conduct of clinical research in children. Aspects of consent, risk-benefit ratios, fair subject selection, and respect for subjects have child-specific concerns. It is only by explicitly recognizing and addressing these child-specific concerns can the conduct of pediatric clinical research achieve and maintain a high level of ethical propriety.