Since a few years, attempts are taken at the application of vagus nerve stimulation in the treatment of severe depression. It appears that the vagus nerve exerts a direct influence on areas of the brain associated with the regulation of mood and increases the level of biogenic amines. What is more, studies have confirmed an increased activity of fronto-orbital and prefrontal cortex, hypothalamus, cingulum and an increased concentration of serotonin and noradrenalin in the CNS and in the cerebro-spinal fluid. Preliminary clinical trials have confirmed the efficacy, good tolerance and safety of this treatment modality, although some objections have been raised whether these promising results were not partly due to the placebo effect. Therefore new, multicenter clinical studies have been designed, enabling an unbiased evaluation of usefulness of this method in the treatment of depression.