Treatment refractory depression (TRMDD) is not uncommon despite adequate anti-depressive treatment trials. Patients who failed adequate trials of anti-depressive therapy including electroconvulsive therapy (ECT) are candidates for stereotactic surgery for mental illnesses. Ablative neurosurgery for TRMDD is performed in 21st century in highly specialized centers, where stereotactic surgeons teamed up with specialized psychiatrists working within stringent governance and ethical guidelines specifically designed for this purpose. The most commonly used procedures today are stereotactic bilateral anterior cingulotomy (BACI) or capsulotomy (BACA). Both thermal coagulation and stereotactic radiosurgery are used to ablate the desired targets. These procedures are safe with good track record. Forty to sixty percent of carefully selected patients with TRMDD are expected to respond or remit within a year of follow up. Response is defined as at least 50 % improvement on validated depression scales, while remission is defined as returning to normal mood and behavior.