A review of electrical stimulation in patients with refractory epilepsy, including animal and human data, shows that there is anatomic and physiologic evidence supporting the role of the thalamus in epilepsy. The most recent reports in patients with refractory epilepsy suggest that deep brain stimulation and cortical electrical stimulation of the anterior thalamic nucleus and hippocampus may reduce seizure frequency in patients with refractory partial and secondarily generalized seizures. This has led to a multicenter, prospective randomized trial called the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE trial) that is currently being conducted at several centers in the United States. There is also a multicenter clinical trial for patients with refractory partial epilepsy treated with a cranially implanted responsive neurostimulator (RNS) system. Preliminary reports from the RNS system feasibility trial (the NeuroPace trial) suggest that electrographic seizures can be detected before they evolve into clinical seizures, and that electrical stimulation of the epileptogenic zone can then terminate the electrographic seizures. The preliminary data in patients using deep brain stimulation of the anterior thalamic nucleus and hippocampus, and cortical stimulation studies of the epileptogenic zone are promising and suggest a reduction in seizure frequency in some patients with refractory partial and secondarily generalized seizures. The exact mechanism of action and the best parameters used during electrical stimulation remain unknown and are the subject of ongoing research.