Background: Children are in a continuous and dynamically changing state of growth and development. A thorough understanding of developmental pharmacokinetics (PK) and pharmacodynamics (PD) is required to optimize drug therapy in children. Data sources: Based on recent publications and the experience of our group, we present an outline on integrating pharmacometrics in pediatric clinical practice to develop evidence-based personalized pharmacotherapy. Results: Antibiotics in septic neonates and immunosuppressants in pediatric transplant recipients are provided as proof-of-concept to demonstrate the utility of pharmacometrics in clinical practice. Dosage individualization based on developmental PK-PD model has potential benefits of improving the efficacy and safety of drug therapy in children. Conclusion: The pharmacometric technique should be better developed and used in clinical practice to personalize drug therapy in children in order to decrease variability of drug exposure and associated risks of overdose or underdose.