Recurrent, spontaneous seizure activity caused by abnormal neuronal firing in the brain is a hallmark of epilepsy, a common chronic neurological disorder. Recent research that has expanded the knowledge of the cellular and molecular mechanisms that modulate neuronal excitability and network activity in the brain provides the development and discovery of antiepileptic drugs (AEDs). AED therapy starts with the selection of the most appropriate drug for individual patient according to a strategic decision based on the risk-benefit ratio. Beyond three generations of AEDs developed over the last 40 years, more effective, better tolerated, disease-modifying pharmacological therapies are still needed to improve seizure outcome and reduce the safet...