With an annual incidence of 50/100,000 people, nearly 1% of the population suffers from epilepsy. Treatment with antiepileptic medication fails to achieve seizure remission in 20-30% of patients. One treatment option for refractory epilepsy patients who would not otherwise be surgical candidates is electrical stimulation of the brain, which is a rapidly evolving and reversible adjunctive therapy. Therapeutic stimulation can involve direct stimulation of the brain nuclei or indirect stimulation of peripheral nerves. There are three stimulation modalities that have class I evidence supporting their uses: vague nerve stimulation (VNS), stimulation of the anterior nuclei of the thalamus (ANT), and, the most recently developed, responsive neurostimulation (RNS). While the other treatment modalities outlined deliver stimulation regardless of neuronal activity, the RNS administers stimulation only if triggered by seizure activity. The lower doses of stimulation provided by such responsive devices can not only reduce power consumption, but also prevent adverse reactions caused by continuous stimulation, which include the possibility of habituation to long-term stimulation. RNS, as an investigational treatment for medically refractory epilepsy, is currently under review by the FDA. Eventually systems may be developed to enable activation by neurochemical triggers or to wirelessly transmit any information gathered. We review the mechanisms, the current status, the target options, and the prospects of RNS for the treatment of medically intractable epilepsy. (c) 2013 Elsevier Inc. All rights reserved.