This paper is a review of the pharmacotherapy of adolescent depression. It begins with a brief discussion regarding the nature of adolescent depression and then critically evaluates the available evidence regarding the efficacy and tolerability of psychotropic intervention as it has, to date, been reported. As the available evidence suggests that tricyclic antidepressants have failed to show efficacy, yet demonstrate significant problems with tolerability and safety, the remainder of the article describes how clinicians should prescribe antidepressants using the serotonin reuptake inhibitors. Areas covered include assessment, treatment initiation, dosing, outcome evaluation, adverse events, and combinations. The review concludes with a discussion of long-term therapy with antidepressant medications.