This chapter reviews the history of invasive and non-invasive procedures for neuropsychiatric conditions, their putative neurobiological foundations, and their effects. The most frequently used procedural interventions are described briefly, including lesional procedures, deep brain stimulation (DBS), vagal nerve stimulation (VNS), electroconvulsive therapy (ECT), and transcranial magnetic stimulation (TMS). The most common lesional interventions include anterior capsulotomy, anterior cingulotomy, subcaudate tractotomy, and limbic leucotomy. VNS was used for the treatment of epilepsy. ECT uses electricity to induce seizures for therapeutic purposes. Cognitive impairments are common among persons receiving ECT, including those arising as a result of the condition at which this treatment is directed, neurological comorbidities, or the effects of treatment. Most patients receiving ECT require continued treatment with medications upon ECT discontinuation. The repertoire of procedural interventions for neuropsychiatric conditions may further expand to include gene therapy, implantable drug delivery systems, and neural transplantation.