Psychosurgery has a controversial history in the treatment of psychiatric disorders, but in recent years there has been mounting evidence for the potential of chronic electrical deep brain stimulation (DBS) of several neuroanatomical targets in managing treatment-resistant depression (TRD), a debilitating mental illness with limited therapeutic options. Achieving optimal clinical outcome with DBS involves characterizing the heterogeneous neuronal circuits responsible for the variable clinical course of depression and selecting nodes within these circuits for stimulation. A number of exciting preliminary studies have used DBS in several discrete brain areas to treat patients with depression. Despite ongoing controversies about the mechanisms responsible for the therapeutic effects of DBS, the clinical results to date show strong promise for this technique as a feasible treatment choice in TRD. The full therapeutic potential of DBS in psychiatric practice will be revealed as future clinical studies focus on careful ethical approaches and the use of long-term placebo controlled comparisons.