The need for critical, well-designed comprehensive clinical pharmacology research in pediatrics that encompasses the age continuum, from the most premature infant through adolescence, may be more important today than ever. New drug regimens often require greater adherence to specific dose guidelines to maximize efficacy and minimize toxic potential. The climate that allowed the propagation of the “therapeutic orphan” concept is now mostly of historical perspective. Nevertheless, the negative impact of this concept continues to linger due to continued propagation of many, now outdated myths surrounding the effective study of optimal drug dosing in pediatrics. Advances in clinical medicine combined with the advances in study design, sampling, and analysis has dramatically improved the paradigm for clinical pharmacology research in infants and children. Capitalizing upon and thoughtfully using these many advances while dispelling these myths will result in greater research focused on optimal drug therapy in pediatric practice.