In the past, worldwide leaders in epilepsy have reiteratively stated that the lack of progress in the field may be explained by the recurrent use of the same molecular targets and screening procedures to identify novel medications. This landscape has changed recently, as reflected by the new Epilepsy Therapy Screening Program and the introduction of many in vitro and in vivo models that could possibly improve our chances of identifying first-in-class medications that may control drug-resistant epilepsy or modify the course of disease. Other milestones include the study of new molecular targets for disease-modifying drugs and exploration of a systems pharmacology perspective to design new drugs.