Clinical trials compare therapeutic interventions. Since the 1960s, proof of efficacy and safety (E&S) is required for drug approval. Regulatory trials became a cornerstone of drug development. In parallel to industry-sponsored regulatory trials, academic trials aim at improving interventions without regulatory concerns. Initially, drugs were approved in humans, and pediatricians used them as well. When toxicities of antibiotics were reported in babies, the American Academy of Pediatrics and pediatric researchers adopted the concept of children as “therapeutic orphans” and demanded separate pediatric studies, resulting eventually in the first US pediatric legislation of 1997 and the EU pediatric legislation, in force since 2007. But pediatric legislation often equalizes administrative age limits with alleged, nonexisting physiological changes at a birthday. Better understanding of the patient’s developing body and consequences for drug treatment encountered an expanding regulatory framework, stronger academic and professional institutions, and the pharmaceutical industry. Pediatric legislation resulted in “pediatric” studies in adolescents that are legally still children, but physiologically already mature. Also separate proof of E&S in younger minors may be exaggerated as they are not another species. All populations require the avoidance of toxicities and adequate dose determination. Demands for age-appropriate pediatric formulations are relevant only in young children, not in the entire “pediatric population.”