Patients with refractory epilepsy present a particular challenge to new therapies. Vagus nerve stimulation (VNS) for the control of intractable seizures has become available since 1989. VNS is a relatively noninvasive treatment. It reduces seizure frequency by > or =50% in 1/3 of patients; an additional 1/3 of patients experience a worthwhile reduction of seizure frequency between 30 and 50%. In the remaining 1/3 of the patients there is little or no effect. Efficacy has a tendency to improve with longer duration of treatment up to 18 months postoperatively. Deep brain stimulation (DBS) or direct electrical stimulation of brain areas is an alternative neurostimulation modality. The cerebellum, various thalamic nuclei, the pallidum, and, more recently, medial temporal lobe structures have been chosen as targets. DBS for epilepsy is beyond the stage of proof-of-concept but still needs thorough evaluation in confirmatory pilot studies before it can be offered to larger patient populations. Analysis of larger patient groups and insight in the mode of action may help to identify patients with epileptic seizures or syndromes that respond better either to VNS or to DBS. Randomized and controlled studies in larger patient series are mandatory to identify the potential treatment population and optimal stimulation paradigms. Further improvements of clinical efficacy may result from these studies.