Epilepsy is a devastating disease, often refractory to medication and not amenable to resective surgery. For patients whose seizures continue despite the best medical and surgical therapy, 3 stimulation-based therapies have demonstrated positive results in prospective randomized trials: vagus nerve stimulation, deep brain stimulation of the thalamic anterior nucleus, and responsive neurostimulation. All 3 neuromodulatory therapies offer significant reductions in seizure frequency for patients with partial epilepsy. A direct comparison of trial results, however, reveals important differences among outcomes and surgical risk between devices. The authors review published results from these pivotal trials and highlight important differences between the trials and devices and their application in clinical use.