Effective therapy for pharmacoresistant epilepsy is an unmet clinical need. Pharmacologically, there are two logical approaches: super-antiictogenic drugs (SAIDs) or antiepileptogenic agents. However, can either of these agents be successfully designed and developed? Designing SAIDs or antiepileptogenics will require applying the techniques of twenty-first century drug design to this ancient "sacred disease." Before this task can be effectively realized, five fundamental needs will first have to be addressed: need for antiepileptogenic drug targets, need for druggable targets for SAIDs, need for new drug molecule platforms, need for new and relevant animal models, and need for innovative funding strategies.