Major depression affects 3 to 5 percent of children and adolescents. Depression negatively impacts growth and development, school performance, and peer or family relationships and may lead to suicide. Biomedical and psychosocial risk factors include a family history of depression, female sex, childhood abuse or neglect, stressful life events, and chronic illness. Diagnostic criteria for depression in children and adolescents are essentially the same as those for adults; however, symptom expression may vary with developmental stage, and some children and adolescents may have difficulty identifying and describing internal mood states. Safe and effective treatment requires accurate diagnosis, suicide risk assessment, and use of evidence-based therapies. Current literature supports use of cognitive behavior therapy for mild to moderate childhood depression. If cognitive behavior therapy is unavailable, an antidepressant may be considered. Antidepressants, preferably in conjunction with cognitive behavior therapy, may be considered for severe depression. Tricyclic antidepressants generally are ineffective and may have serious adverse effects. Evidence for the effectiveness of selective serotonin reuptake inhibitors is limited. Fluoxetine is approved for the treatment of depression in children eight to 17 years of age. All antidepressants have a black box warning because of the risk of suicidal behavior. If an antidepressant is warranted, the risk/benefit ratio should be evaluated, the parent or guardian should be educated about the risks, and the patient should be monitored closely (i.e., weekly for the first month and every other week during the second month) for treatment-emergent suicidality. Before an antidepressant is initiated, a safety plan should be in place. This includes an agreement with the patient and the family that the patient will be kept safe and will contact a responsible adult if suicidal urges are too strong, and assurance of the availability of the treating physician or proxy 24 hours a day to manage emergencies.