This paper, based on the 4th Annual Hoyer Lecture presented at the 2006 annual meeting of the American Epilepsy Society, first provides a general view of the current limitations in therapies aimed at achieving the goal of "no seizures, no side effects" for patients living with epilepsy. Some of the seminal discoveries in epilepsy research over the past 100 years are then reviewed, with an emphasis on the pivotal role of basic and clinical/translational science in leading the way to new and effective means for diagnosing and treating for epilepsy. The paper concludes with a view of the future course of epilepsy research. Scientific advances will increasingly rely on the collaboration of multidisciplinary teams of researchers using the analytic and storage capabilities of machines, and linked together by communication tools such as the Internet and related technologies.