During the last decade vagus nerve stimulation (VNS) was established as a "third way" in the treatment of epilepsies beside of pharmacotherapy and epilepsy surgery. Given the moderate anticonvulsant effects (responder rates in controlled studies of about 30%, very low rate of seizure-free patients) possible psychological effects are relevant for the indication. The present review reports the evidence for cognitive, emotional and quality of life related effects of VNS. In proper clinical pre-post studies (controlled, randomised, valid measures, sufficient sample size; e.g., Dodrill and Morris [18]) no VNS-specific psychological effects could be obtained (observation interval: about 3 months). Smaller or uncontrolled studies reported positive psychological effects which, however, due to the design may not be attributed to VNS. Experimental on-off studies with clinical output current (> 0.75 mA) either failed to reveal cognitive effects of acute stimulation or obtained evidence for discrete VNS-associated functional disturbance. With low amplitude stimulation (0.5 mA) cognitive and mnestic effects could be revealed in both animals and patients. These effects were improvements of object recognition, encoding, and decision making but also impairment of creative reasoning. The pattern of findings is consistent with the notion that low amplitude VNS (0.5 mA) may activate the locus ceruleus and, by this, may achieve the well-known noradrenaline-associated cognitive and mnestic effects. Other effects of VNS might be achieved or increased by this mechanism. © Steinkopff-Verlag 2006.