Major depressive disorder occurs in approximately 2% of prepubertal children and 5% of adolescents. Studies investigating the pharmacotherapy of early-onset major depressive disorder in these young patients have been inconclusive. Early open trials and anecdotal experience suggested a beneficial role for antidepressant therapy. Double-blind placebo-controlled trials have failed to demonstrate the robust response seen in adults, but the studies have been small and concerns have been raised regarding methodology. Nevertheless, the significant morbidity associated with depressive disorders and the positive open trial experiences with antidepressants have led to the recommendation that antidepressants be used early in life when a patient presents with symptoms of a depressive disorder and has significant functional incapacity because of these symptoms. This article will review the studies of antidepressant efficacy in juvenile-onset major depressive disorder and then propose a pharmacotherapy model.