Significant advances have been made in the treatment of epilepsy over the past decades. However, despite the development of various novel antiepileptic drugs, about one third of patients with epilepsy is resistant to current pharmacotherapies. Even in patients in whom pharmacotherapy is efficacious, current antiepileptic drugs do not seem to affect the progression or underlying natural history of epilepsy. Furthermore, there is currently no drug available which prevents the development of epilepsy, e.g. after head trauma. Thus, there are at least three important goals for the future. (1) Better understanding of processes leading to epilepsy, thus allowing to create therapies aimed at the prevention of epilepsy in patients at risk; (2) improved understanding of biological mechanisms of pharmacoresistance, allowing to develop drugs for reversal or prevention of resistance; and (3) development of disease-modifying therapies, inhibiting the progression of epilepsy. The ultimate goal would be a drug combining these three properties, thus resulting in a complete cure for epilepsy. In this review, the current status of antiepileptic therapies is critically assessed, and innovative approaches for future therapies are highlighted.