Neurostimulation is an emerging treatment for neurological diseases. Electrical stimulation of the tenth cranial nerve or vagus nerve stimulation (VNS) has become a valuable option in the therapeutic armamentarium for patients with refractory epilepsy. It is indicated in patients with refractory epilepsy who are unsuitable candidates for epilepsy surgery or who have had insufficient benefit from such a treatment. Vagus nerve stimulation reduces seizure frequency with > 50% in 1/3 of patients and has a mild side effects profile. Research to elucidate the mechanism of action of vagus nerve stimulation has shown that effective stimulation in humans is primarily mediated by afferent vagal A- and B-fibers. Crucial brainstem and intracranial structures include the locus coeruleus, the nucleus of the solitary tract, the thalamus and limbic structures. Neurotransmitters playing a role may involve the major inhibitory neurotransmitter GABA but also serotoninergic and adrenergic systems. This manuscript reviews the clinical studies investigating efficacy and side effects in patients and the experimental studies aiming to elucidate the mechanims of action.