Approximately one third of children with epilepsy have persistent seizures despite trials of multiple antiepileptic medications. For some of these patients, epilepsy surgery may provide freedom from seizures. However, in many cases, epilepsy surgery is not a viable treatment option. Nonpharmacological approaches are a useful adjunct to help manage seizures in these children. This review examines the role of vagus nerve stimulation, the ketogenic diet, and various forms of EEG biofeedback therapy in children with intractable epilepsy. Although the mechanism of action is not known precisely for any of these adjunctive therapies, they add an important and evolving dimension to the management of difficult to control epilepsy in children. In addition, pyridoxine-dependent seizures are discussed as an example of an etiology of refractory seizures that responds well to replacement therapy.