Interest in using neuromodulation to treat psychiatric disorders is rapidly increasing. The development of novel tools and techniques, such as deep brain stimulation (DBS), increases precision and minimizes risk. This article reviews the history of psychosurgical interventions and recent developments of DBS to provide a framework for understanding current options and future goals. We begin by discussing early approaches to psychosurgery, focusing on the widespread use of lobotomy and the subsequent backlash from the public and professionals in the field. Next, we discuss the development of stereotaxis. This technique allows for more targeted, precise interventions that produce discrete subcortical lesions. We focus on four stereotactic procedures that were developed using this technique: cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. We subsequently review contemporary theory and approaches with relevance to psychosurgery. We discuss the systems and neurocircuitry that are thought to be involved in psychiatric illness and provide targets for intervention. This discussion includes presentation of basal ganglia thalamocortical pathophysiology including cortico-striato-thalamo-cortical loops. We focus the discussion on two psychiatric disorders that have been targets of neurosurgical interventions: obsessive-compulsive disorder and mood disorders such as major depressive disorder. Evidence from studies of DBS in psychiatric disorders, including efficacy and tolerability, is reviewed. Finally, we look to the future, exploring the possibilities for these approaches to increase understanding, transform societal views of mental illness, and improve treatment. [Copyright &y& Elsevier]