Vagus nerve stimulation (VNS) for epilepsy has been available in the United States for 8 years. Pivotal randomized, blinded clinical trials leading to FDA approval in patients age 12 and older with refractory partial seizures have not been performed for other age groups or epilepsy syndromes. This practical review takes stock of the current information about VNS use and efficacy in various types of epilepsy. We review the evidence for commonly used stimulation parameters, end of battery life, predictors of response including duration of epilepsy, seizure type/epilepsy syndrome, bihemispheric seizures, age at implant, and prior cranial surgery. We review adverse events and VNS effects on respiratory patterns, cardiac function, and mood and behavior. With the recent U.S. approval of VNS for treatment-resistant depression, we anticipate that lessons learned from treating patients with epilepsy will be useful to physicians using VNS to treat patients with depression and possibly other conditions.