Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome and is often associated with pharmacoresistance. Patients with pharmacoresistant TLE may be candidates for epilepsy surgery, and anterior temporal lobectomy if indicated is the most effective known treatment and has the best chance of a seizure-free outcome. For many patients with TLE, epilepsy surgery is not an option, for example when the seizure onset zone co-localizes with eloquent brain function and cannot be resected, or the seizure onset zone is not well localized, or when seizures independently originate from both temporal lobes. For many of these patients, electrical stimulation is a viable treatment option, such as electrical stimulation of the hippocampus, or temporal neocortex, or thalamus. Animal and clinical studies in humans have demonstrated electrical stimulation is an effective and safe treatment. Moreover, successful application of responsive neurostimulation system in the treatment of temporal lobe epilepsy has been reported recently. This review is intended to provide a comprehensive review of the modern history of electrical stimulation of the hippocampus for the treatment of refractory medial temporal lobe epilepsy and discuss the anatomical basis, validity, side effects, stimulation paradigm and mechanism of hippocampus stimulation and the responsive electrical stimulation trials. (C) 2014 Elsevier Inc. All rights reserved.