Pediatric depression is a prevalent and recurrent condition that persists into adulthood and carries significant impairment, morbidity, and risk of mortality. Although there has been a surge of pediatric antidepressant studies in recent years, depression remains largely understudied, unrecognized, and untreated in children and adolescents. Few antidepressant trials have yielded positive results in pediatric depression. Regulatory agencies recently issued warnings against the use of selective serotonin reuptake inhibitors and newer antidepressants in depressed children and adolescents because of a possible link between their use and the appearance or worsening of suicidal ideation or attempts. The authors review data on efficacy and safety of antidepressants for the treatment of pediatric depression to provide treating clinicians with a basis on which to guide their treatment recommendations.