The goal of antiepileptic therapy is to achieve long-term seizure freedom with minimal or no adverse effects. Current evidence suggests that in many patients who have failed two appropriate antiepileptic drugs (AEDs) because of lack of efficacy, the chance of subsequent seizure freedom with further drug manipulation is low (reports ranging from as little as a few percent to nearly one-fourth of patients). Achieving this may require repeated drug manipulations. Surgery, in appropriately selected candidates, may render up to 70% of patients seizure-free when temporal resection is done, although frontal resection may have only a 25% yield. Both courses of actions (further drug trials and surgery) are associated with a plethora of potential adverse outcomes. Therefore, it is recommended that such patients be promptly referred to an epilepsy center for a comprehensive review of the diagnosis and management, which may include initial evaluation for surgery. Because presurgical evaluation and surgery itself may entail discomfort and risk, the decision to offer surgical treatment requires individual risk-benefit analysis that includes an assessment of possible success with additional trials of medication.