Effective new antiepileptic drugs (AEDs) are needed for the treatment of those with refractory epilepsy. However, with the growing number of these drugs being licensed and marketed, a rational approach to the treatment of epilepsy is becoming essential. New AED trials can determine appropriate use of AEDs but ultimately fail to determine the best use of AEDs and their exact role in treating patients. New AED trials rarely use clinically applicable measures of efficacy, and it is difficult to extrapolate the data from populations used in AED trials to the wider population of patients with epilepsy. Furthermore, AED trials ignore the factors that are most likely to determine prognosis: the etiology, seizure types, and epilepsy syndrome. To resolve these issues, we need large multicenter studies in well-defined populations with well-characterized seizures, epilepsy syndromes, and etiologies. Being seizure free should be the primary measure of efficacy rather than meta-analyses and guidelines based upon incomplete data.