Treatment-resistant depression affects at least 1-3% of the US population. This article reviews the current state of focal neuromodulation therapies for treatment-resistant depression, focusing on those treatments published clinical data. These include transcranial magnetic stimulation, transcranial direct current stimulation, magnetic seizure therapy, vagus nerve stimulation, direct cortical stimulation, and deep brain stimulation among others. Of these, only two (transcranial magnetic stimulation and vagus nerve stimulation) currently have US Food and Drug Administration approval for the treatment of depression.