In 1968, Dr. Harry Shirkey wrote the following: “By an odd and unfortunate twist of fate, infants and children are becoming therapeutic or pharmaceutical orphans.” His observation was based on the very low number of drugs that were appropriately labeled for use in children caused by laws regulating drug manufacturing, testing, and distribution, which were, paradoxically, often introduced as a response to therapeutic misadventures in children. These early regulatory laws advocated for the practice of restriction as the primary means to maximize drug safety in pediatric patients, resulting in the exclusion of pediatric patients from the study of therapeutic drugs, many of which were intended for pediatric use. Consequently, these laws resulted in drug labeling practices that included warnings for most new drugs stating that because of inadequate (or nonexistent) data in children, the majority of drugs were not recommended for use in children. This led Dr. Shirkey in 1968 to issue a call to academia, industry, and government to actively take the responsibility for including children in the development programs of drugs intended for pediatric use. Despite a profound unmet need, little progress was made in almost two decades after this call to action was issued.