Depression is increasingly recognized as an illness that causes functional impairment and diminished quality of life for all age groups, including children. One to two percent of children and between 4% and 8% of adolescents meet Diagnostic Statistical Manual of Mental Disorders(4th ed.) (DSM-IV-TR) criteria for major depression. Psychotherapy, particularly cognitive-behavioral therapy, is effective, with 70% response rates. Antidepressants are effective according to limited controlled trials; however, concern exists over the gap between research and clinical practice, as most antidepressants are not well-studied in youth. Nevertheless, pharmacotherapy has gained greater acceptance in pediatric psychiatry, and prescriptions for antidepressants in youth have increased dramatically over the past 5 to 10 years. In 1995, 1.08 million selective serotonin reuptake inhibitor prescriptions were written for children and adolescents. Scientific evidence for the safety and effectiveness of antidepressants in youth is reviewed along with data on nondrug interventions such as cognitive-behavioral therapy. Recommendations for promoting the safe and effective management of depression in children and adolescents is provided.