Objective: Methylphenidate (MPH) is the most often prescribed medication for treatment of ADHD. However, many of its specific cellular and molecular mechanisms of action, as well as developmental consequences of treatment, are largely unknown. This review provides an overview of current understanding of MPH efficacy, safety, and dosage in adult and pediatric ADHD patients, as well as adult animal studies and pioneering studies in juvenile animals treated with MPH. Method: A thorough review of the current literature on MPH efficacy and safety in children, adults, and animal models was included. Results of studies were compared and contrasted. Results: While MPH is currently considered safe, there is a lack of knowledge of potential developmental consequences of early treatment, as well as differences in drug actions in the developing versus mature brain system. Conclusion: This review emphasizes the need for further research into the age-dependent activities and potency of MPH, and a need for tighter control and clinical relevance in future studies. ( J. of Att. Dis. 2012; XX(X) 1-XX)