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To describe the most important issues a clinician must consider whenever selecting and administering antiepileptic drugs (AEDs). There is no available algorithm that identifies how to individualize selection of AEDs. Proper selection and administration can make an enormous difference in both effectiveness and tolerability.Many principles of AED selection remain unchanged. Selection of AEDs must be based on understanding of epilepsy syndrome and seizure type, comorbidities, risk of adverse events, as well as on patient characteristics such as age and sex. Recently personalized medicine through genetics has become a reality for a subset of patients, to select optimal drugs, and avoid side effects. Selection of AEDs for women can be performed to avoid teratogenic agents, as safer AEDs have been identified. There is evidence supporting use of controlled release AED formulations, whenever available. Whenever selecting an optimal dose, physicians should attend to the principle of ‘start low, go slow.’ ‘Intelligent use’ includes not only appropriate drug selection, but also optimal and individualized dose adjustment. Drug optimization involves appropriate titration, dose schedule, individualization of therapeutic range and rescue planningIntelligent drug use, individualized to patient characteristics, can guide management for optimal seizure control.