Recent evidence suggests that medically resistant epilepsy can be identified if seizures persist despite adequate doses of 2 appropriate first-line antiepileptic drugs (AEDs). Patients with medically resistant epilepsy should have their seizures carefully characterized in order to confirm their diagnosis, select treatment, and assist in determining prognosis. Patients should be counseled about factors that aggravate epilepsy and the importance of adhering to treatments. Physicians should carefully inquire about side effects and alter therapy to eliminate or minimize these symptoms. Uncontrolled seizures cause injuries, disability, and increased mortality, so surgery should be considered as soon as seizures are proven to be medically resistant. Patients with incomplete response to AEDs and who are not surgical candidates may benefit from additional medication trials or from palliative nonmedical therapies, such as vagal nerve stimulation.