Alternative methods, for the treatment of medically refractory epileptic patients, who cannot be treated by resective surgery, such as chronic deep brain neurostimulation, are under development. Such methods have been used in the cerebellum, various thalamic nuclei, and in the caudate nucleus. In Grenoble, encouraged by the suppressive effects of pharmacological or electrical inhibition of the STN on different types of seizure in animal models of epilepsy, and by our experience with STN high frequency stimulation (HFS) in patients with movement disorders, we have evaluated the high frequency stimulation of the subthalamic nucleus (STN HFS). STN HFS was performed in five patients suffering from medically intractable seizures and considered unsuitable for resective surgery. A 67% to 80% reduction in seizure frequency was observed in three patients, with a partial symptomatic epilepsy of the central region. An additional patient suffering from severe myoclonic epilepsy (Dravet syndrome) also responded to STN HFS, with a weaker reduction of seizure frequency. The fifth patient who suffered from an autosomal dominant frontal lobe epilepsy with insulo-frontal seizures did not show any improvement. These results suggest that stimulation of STN could be a promising treatment for patients with drug-resistant epilepsy who would not benefit from conventional surgery.