Repetitive transcranial magnetic stimulation (rTMS) is a new brain intervention that modulates neuronal activity in discrete cortical regions and associated neural circuits by the noninvasive induction of intracerebral currents. Single pulse transcranial magnetic stimulation (TMS) is a unique method for mapping brain-behavior relations and functional connectivity, and probing cortical excitability. Repeated pulses are used in rTMS as a potential therapy. rTMS modulates activity in discrete cortical areas that, in turn, impact on specific pathways or brain networks. This spatial specificity may provide advantages by producing clinical improvement with reduced or minimal side effects. Standard pharmacologic interventions are limited by the inability to restrict their action to discrete brain regions. In addition to the spatial specificity, rTMS differs from pharmacologic interventions in the temporal domain. Medications act continuously in altering the physiology of brain and other organs, especially when steady-state levels are reached. In contrast, rTMS is delivered in a punctate fashion, akin to electroconvulsive therapy. The remark-able brevity of the TMS pulse (-200 μs) results in a total exposure to a time-varying magnetic field of only a few seconds over an entire rTMS treatment course, despite weeks of daily treatment sessions. This article focuses on the therapeutic potential of TMS for the acute treatment of depression, a domain that has been the subject of a large number of single site, small sample studies. Virtually all reviewers of this preliminary work have concluded that rTMS has antidepressant properties, with all meta-analyses indicating that there is a large effect size for symptom change when compared to sham treatment. Across the literature using active TMS, the median level of symptom change on the Hamilton Rating Scale for Depression has been on the order of 30%; approximately 10% of those receiving sham rTMS responded. Recent effectiveness data suggest that rTMS in clinical settings has similar effects as in the published controlled trails. Drastically improving on prior studies, an industry-sponsored multisite TMS trial designed for Food and Drug Administration submission is near completion, and a rigorous four-site National Institute of Mental Health-sponsored treatment trial is underway.