Electrical stimulation of the vagal nerve (VNS) has become an established method for treating medically refractory epilepsies. From animal experiments it is well known that depending on the stimulation intensity VNS can elicit both inhibition and facilitation of nociception. Recent physiologic investigations demonstrated a similar influence of VNS on pain perception in patients treated by chronic VNS. However, in humans, a more marked effect was shown for the pain inhibition which is probably mediated by neurobiochemical mechanisms. These findings are discussed in consideration of the physiologic mechanisms underlying the modulation of pain and seizures by VNS known from animal studies. First reports of attenuation of chronic pain by VNS indicate that the method might be an option for pain treatment in the future.