Electroconvulsive therapy (ECT) is the most effective acute treatment for a major depressive episode. However, some patients do not achieve symptomatic remission with ECT, many patients cannot tolerate the cognitive side-effects, and the relapse rate over several months is high. In an effort to find treatments that are as effective as, or more effective than, ECT, better tolerated, and associated with long-term maintenance of antidepressant effects, increasing attention has focused on a variety of brain stimulation therapies, including: vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, and deep-brain stimulation. In this chapter, we review the history, strengths, and weaknesses of ECT as a treatment for depression, followed by a detailed discussion of the available data supporting safety and efficacy of other brain stimulation therapies. As research on these novel treatment modalities progresses, it is hoped that improved treatment for depression will be achieved. Additionally, these modalities offer unique opportunities to study the neurobiology of disease.