Epilepsy in elderly patients, compared with the younger adult population, differs in etiology, clinical presentation, and prognosis. Challenges in the pharmacologic treatment of epilepsy in the elderly include the following: the physiologic changes associated with aging; adverse events to which the elderly are especially vulnerable; the increased risk for these patients, who are often taking multiple medications; and toxicity from drug-drug interactions. This article presents data on efficacy and safety from clinical trials of newer antiepileptic drugs (AEDs) in elderly patients compared with older AEDs. We discuss the implications of the findings using newer-generation AEDs in the Veterans Affairs Cooperative Study (VACS) #428 in order to educate physicians involved in choosing appropriate AEDs for older patients. In the elderly patient population, an optimal treatment outcome of seizure control with minimal or no adverse events is dependent on the well-informed choice of an AED by a physician.