Early in the last century, neuroscientists initially speculated that it might be possible to influence brain activity and associated behaviours by stimulating the vagus nerve in the neck. Several animal studies pointed to this possibility. In the 1980s, Zabara discovered that vagus nerve stimulation (VNS) could reduce or eliminate seizures in dogs. His discovery led to enhanced methods of direct VNS and the development of an implantable device for human VNS. VNS is now an accepted long-term treatment for epilepsy, used by over 15000 patients worldwide. Many have wondered whether VNS could treat other neuropsychiatric disorders. This paper reviews the neurobiology involved in VNS, highlights the VNS clinical findings to date, and discusses potential VNS research opportunities for both clinical and basic investigators. Comments on the clinical utility of VNS in actual clinical practice are provided.