Major depression is a serious illness in children which adversely effects their social, academic, and emotional development. It is essential to identify safe and effective medication for the treatment of this disorder in youths. Only some selective serotonin reuptake inhibitors (citalopram, fluoxetine, sertraline) have demonstrated superiority to placebo on primary outcome measures in acute controlled treatment trials. This article will review acute efficacy studies as well as long-term studies of antidepressants for the treatment of childhood depression. Treatment recommendations are discussed and the issue of suicidality and antidepressants are addressed.