Objective: To revise and update consensus guidelines for medication treatment algorithms for childhood major depressive disorder based on new scientific evidence and expert clinical consensus when evidence is lacking. Method: A consensus conference was held January 13-14, 2005, that included academic clinicians and researchers, practicing clinicians, administrators, consumers, and families. The focus was to review, update, and incorporate the most current data to inform and recommend specific pharmacological approaches and clinical guidance for treatment of major depressive disorder in children and adolescents. Results: Consensually agreed on medication algorithms for major depression (with and without psychosis) and comorbid attention-deficit disorders were updated. These revised algorithms also incorporated approaches to address issues of suicidality, aggression, and irritability. Stages 1, 2, and 3 of the algorithm consist of selective serotonin reuptake inhibitor and norepinephrine serotonin reuptake inhibitor medications whose use is supported by controlled, acute clinical trials and clinical experience. Recent studies provide support that selective serotonin reuptake inhibitors in addition to fluoxetine are still encouraged as first-line interventions. The need for additional assessments, precautions, and monitoring is emphasized, as well as continuation and maintenance treatment. Conclusions: Evidence and expert clinical consensus support the use of selected antidepressants in the treatment of depression in youths. The use of the recommended antidepressant medications requires appropriate monitoring of suicidality and potential adverse effects and consideration of other evidence-based treatment alternatives such as cognitive behavioral therapies. (Contains 1 table and 2 figures.)