Vagus nerve stimulation (VNS) is an established neurostimulation therapy used to treat refractory epilepsy. The effect of acute or chronic VNS on the postictal state as a separate entity is seldom reported in clinical or experimental studies. Apart from its antiseizure effects, VNS has several other beneficial effects. These effects may be of particular benefit for patients with postictal neuropsychiatric symptoms. The hypothesized mechanisms underlying the initiation and sustainment of the postictal phase, to some extent, overlap with mechanisms involved in the seizure-suppressing effects of VNS as well as other neurological and psychotropic effects of VNS. Both the clinical symptoms and the basic research hypotheses of the postictal state show similarities with clinical effects induced by VNS and its underlying mechanisms of action.