This article reviews existing research pertaining to antidepressant medications, psychotherapy, and their combined efficacy in the treatment of clinical depression in youth. Based on this review, we recommend that youth depression and its treatment can be readily understood from a social-psycho-bio model. We maintain that this model presents an alternative conceptualization to the dominant biopsychosocial model, which implies the primacy of biological contributors. Further, our review indicates that psychotherapy should be the frontline treatment for youth with depression and that little scientific evidence suggests that combined psychotherapy and medication treatment is more effective than psychotherapy alone. Due primarily to safety issues, selective serotonin reuptake inhibitors should be initiated only in conjunction with psychotherapy and/or supportive monitoring.