Chronic and recurrent major depressive episodes are associated with significant morbidity and mortality, and available treatments often are ineffective or only partially effective. This issue is of particular concern in children and adolescents, because major affective disorders often begin early in life and follow a chronic, progressive course. Because the current treatment armamentarium for depressive episodes in this age group is limited, the investigation for safe and effective treatment interventions is warranted. Vagus nerve stimulation therapy has proven safety, tolerability, and efficacy in the treatment of epilepsy, and early findings suggest safety and efficacy in the treatments of adults with chronic and recurrent treatment-resistant mood disorders. This intervention also holds promise as a potential treatment in children and adolescents, although research is currently lacking.