Considerable progress in the pharmacotherapy of epilepsy has been witnessed during the 20th century. However, despite the development of various antiepileptic drugs, about a third of patients are resistant to current pharmacotherapies. Even in patients in whom pharmacotherapy is efficacious, current antiepileptic drugs do not affect the progression or underlying natural history of the condition. Furthermore, currently there are no drugs available that prevent the development of epilepsy following, for example, head trauma. The rapid expansion of information about the cellular, molecular and genetic mechanisms of epilepsy is expected to lead to more effective therapies, prevention or even a cure for different types of epilepsy. In this article, I assess the current status of antiepileptic therapies and highlight innovative approaches for future treatments.