An increase in the number of well-conducted pharmacokinetic-pharmacodynamic (PKPD) pharmacology studies in children has replaced older methodologies such as extrapolation from adult or nonhuman data. While neonates, infants, and children have different psychology, social structure, behavior, and disease spectrum from adults, they also share many similarities. Growth and developmental aspects account for major differences between neonates and infants and adults. Once out of infancy, body size alone can account for many of the pharmacokinetic differences between children and adults. Pharmacodynamic factors that may influence response in early life remain poorly defined. Most PK and PD differences occur in the first few years of postnatal life with major changes occurring during the neonatal period that are mature by the end of infancy (i.e., 2 years of age). Knowledge of pediatric PKPD, changes seen during growth and maturation, and drug adverse effect spectrum are essential for dosing sedatives in children.