Childhood obesity is emerging as a major public health threat, with adverse implications on the health of individuals and long-term costs to society. Family-based lifestyle interventions with behavioral modification, diet and exercise form the mainstay of treatment. Pharmacologic treatment may be considered in selected subjects, especially in the presence of significant and severe comorbidities, when lifestyle intervention has failed to achieve weight reduction. Orlistat and sibutramine are FDA-approved for treatment of pediatric obesity; metformin may be considered in the presence of clinically significant insulin resistance. Evidence is lacking on the appropriate duration of medical therapy and optimal combination with lifestyle intervention. Lack of coverage of medications by insurance and high out-of-pocket costs may be limiting factors to some families. Adverse effects necessitate careful monitoring and may lead to discontinuation of medication. Pharmacologic agents with novel mechanisms of action offer hope of improved efficacy, tolerability and safety.