Vagus nerve stimulation is a palliative treatment for medically intractable epilepsy. This treatment reduces the frequency and severity of seizures refractory to antiepileptic drugs. Implanted generator and helical electrodes electrically stimulate the left vagus nerve at the neck chronically and intermittently. This was the first electrostimulation therapy clinically introduced for epilepsy. This treatment approach is supported by randomized double-blind trials even though the anti-seizure effect of vagus nerve stimulation is palliative and not curative. In Western countries, particularly the United States, this therapy has become an important alternative treatment for a subpopulation of patients with drug-resistant seizures who are not good candidates for craniotomy. In Japan, vagus nerve stimulation therapy was finally approved in January 2010 and has been covered by public health insurance since July 2010. Here, the author reviews the history, efficacy, and safety of this treatment, surgical anatomy and physiology of the vagus nerve, and the putative mechanisms underlying inhibition of epileptic seizures and accompanying effect on the central nervous system. Further experimental and clinical studies regarding this treatment approach are required to elucidate the detailed mechanism of action, to clarify the predicting factors of favorable outcome, and to scientifically confirm the anti-seizure effect in children and in generalized seizures and the efficacy in improvement of cognitive function, development, and quality of life.