Depression is one of the most disabling conditions in the world. In many cases patients continue to suffer with depressive disorders despite a series of adequate trials of medication and psychotherapy. Neuromodulation treatments offer a qualitatively different modality of treatment that can frequently prove efficacious in these treatment-refractory patients. The field of neuromodulation focuses on the use of electrical/electromagnetic energy, both invasively and noninvasively, to interface with and ultimately alter activity within the human brain for therapeutic purposes. These treatments provide another set of options to offer patients when clinically indicated, and knowledge of their safety, risks and benefits, and appropriate clinical application is essential for modern psychiatrists and other mental health professionals. Although neuromodulation techniques hold tremendous promise, only three such treatments are currently approved by the United States Food and Drug Administration (FDA) for the treatment of major depressive disorder: electroconvulsive therapy (ECT), vagus nerve stimulation (VNS), and repetitive transcranial magnetic stimulation (rTMS). Additionally, numerous other neurostimulation modalities (deep brain stimulation [DBS], magnetic seizure therapy [MST], transcranial electric stimulation [tES], and trigeminal nerve stimulation [TNS]), though currently experimental, show considerable therapeutic promise. Researchers are actively looking for ways to optimize outcomes and clinical benefits by making neuromodulation treatments safer, more efficacious, and more durable.