Schizophrenia is a psychiatric disorder associated with significant morbidity and mortality. Although antipsychotic medications and electroconvulsive therapy can be used to manage the clinical symptoms of schizophrenia, a substantial portion (10%–30%) of patients do not clinically respond to these treatments or cannot tolerate the side effects. Recently, deep brain stimulation (DBS) has emerged as a promising safe and effective therapeutic intervention for various psychiatric disorders. Here, the authors explore the utility of DBS of the habenula (HB) in the clinical management of 2 young adult male patients with severe, chronic, and treatment-resistant schizophrenia. After HB DBS surgery, both patients experienced improvements in clinical symptoms during the first 6 months of treatment. However, only 1 patient retained the clinical benefits and reached a favorable outcome at 12-month follow-up. The symptoms of the other patient subsequently worsened and became so profound that he needed to be hospitalized at 10-month follow-up and withdrawn from further study participation. It is tentatively concluded that HB DBS could ultimately be a relatively safe and effective surgical intervention for certain patients with treatment-resistant schizophrenia.