Ever since the introduction of chemical and electrical convulsive treatment for psychiatric disorders in the 1930s and 1940s, biological techniques have been used extensively in the amelioration of a variety of psychiatric disorders. Techniques of recent vintage have included transcranial magnetic stimulation, deep brain stimulation and vagus nerve stimulation (VNS). Since VNS attenuates seizures in animal models, the treatment was initially developed and approved by the FDA for treatment of drug-resistant partial-onset epilepsy. Additional data, including the known neuroanatomy of the vagus nerve, effects of VNS on monoamines and mood improvement in patients with epilepsy who were treated with VNS, provided a rationale for further investigation in patients with primary mood disorders. VNS has been administered acutely for 10 weeks to 60 patients with treatment-resistant depression. Longer-term follow-up data has been analysed for the first 30 patients. Response rates have been at least 30% in the acute study. Similar to findings in epilepsy and in contrast to the usual results of long-term medication trials, longer term data regarding symptomatic and functional outcomes of depressed patients receiving VNS continue to look promising. As opposed to electroconvulsive therapy, VNS is not associated with cognitive impairment. These results have led to approval of VNS for the treatment of resistant depression (unipolar or bipolar) in both Europe and Canada. Currently, a pivotal double-blind acute study is underway in the US.