The current evidence-based data on efficacy, safety, and administration of the 7 new antiepileptic drugs (AEDs) approved over the past 10 years by the US Food and Drug Administration to treat new-onset and refractory epilepsy in children and adults is summarized based on the recent American Academy of Neurology (AAN) guidelines. The clinical trial work still necessary as well as areas where such research would not be informative and those in which nonevidence-based strategies are needed are highlighted in efforts to provide clinicians with the most up-to-date information on treatment regimens for patients with epilepsy. The limited amount of data currently available on these newer AEDs and the existence of traditionally efficacious medications complicate therapeutic decision-making for the clinician. Neurologists are encouraged to integrate the AAN guidelines with clinical experience, opinion, and other considerations of special populations until an exhaustive set of guidelines is available for a wide variety of seizure types.