Some epilepsy patients quickly develop resistance to antiepileptic drugs (AEDs). We report a case of a patient with refractory epilepsy with daily seizures who initially responded to levetiracetam daily therapy, but then returned to baseline seizure frequency. However, when levetiracetam was given once weekly, the patient had significantly fewer seizures on the day of and after administration. These results suggest a useful treatment strategy for patients with refractory epilepsy who have developed resistance to AEDs.