Neurostimulation is a recent development in the treatment of epilepsy. Vagus nerve stimulation (VNS), the only approved neurostimulation therapy for epilepsy to date, has proved to be a viable adjunctive treatment option. The exact mechanism of action of VNS is not fully understood. In 2 randomized double-blind trials, seizure frequency declined approximately 30% after 3 months of treatment. Long-term follow-up studies suggest that response improves over time, with approximately 35% of patients experiencing a 50% reduction and 20% experiencing a 75% reduction in seizure frequency after 18 months of treatment. Unfortunately, the number of patients rendered medication-free and seizure-free with VNS is low. Vagus nerve stimulation is best viewed as an option for patients who are not surgical candidates or who hesitate to take the risk of surgery yet continue to have seizures despite maximal medical therapy. Stimulation of other regions of the central nervous system for treating epilepsy, including the anterior and centromedian nuclei of the thalamus, the hippocampus, the subthalamic nucleus, and the cerebral neocortex, is currently under investigation. We review the history, proposed mechanisms of action, clinical trials, adverse effects, and future direction of VNS and other modalities of neurostimulation therapy for epilepsy.