Abstract: The American Epilepsy Society 2004 Annual Course, entitled “Genetics and Epilepsy Syndromes" took place in New Orleans on Sunday, December 5, 2004 at the AES Annual Meeting and is summarized in this supplement. The course addressed current knowledge on the genetics of epilepsy and its role in epilepsy diagnosis, treatment, and pathophysiological understanding of the disease state. Recent developments in genetics were reviewed and new findings were explored. This year's course once again included a series of case presentations designed to highlight important concepts and novel applications of modern genetic information. These manuscripts were developed by speakers at the course based on their lectures. Drs. Tracey Milligan and Edward Bromfield begin with a case presentation illustrating the complexities of genetic influence on complex diseases, in this case migraine and epilepsy. Dr. Ruth Ottman then presents a comprehensive discussion the genetic analysis of complex diseases, including a review of some of the newest techniques of genetic analysis. Dr. Prakash Kotagal presents a case of linear nevus syndrome, and then Dr. Helen Cross discusses the spectrum of neurocutaneous syndromes associated with epilepsy, many of which are genetically determined. Next, Drs. Melodie Winawer and Shlomo Shinnar present a case illustrating the difficulties in genetic counseling and review the issues encountered in using genetic information to predict individual susceptibility to seizures. Following Dr. Martin Brodie's presentation of two cases of epilepsy, one sensitive to medications and the other resistant, Dr. Sanjay Sisodiya reviews current knowledge on the genetics of drug resistance. The Supplement continues with a case of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) presented by Drs. Arthur Grant and Blanca Vazquez, followed by a review of neonatal epilepsy syndromes with special attention to GEFS+ by Dr. Ingrid Scheffer et al. Next, Dr. Mohamad Mikati presents a case illustrating issues in the understanding of the genetics of idiopathic primary epilepsy. Dr. Daniel Burgess then discusses potential mechanisms whereby specific mutations produce characteristic clinical phenotypes and reviews the challenges encountered in using genetic information to understand pathophysiology and develop rational treatment. The course concludes with the presentation of a case of Familial Temporal Lobe Epilepsy with Auditory Features by Dr. Fernando Cendes et al., followed by a review of genetically determined partial epilepsy syndromes by Drs. Fred and Eva Andermann and colleagues. The goal of the symposium was to educate participants on the state of the art of genetic research in epilepsy and to highlight both the challenges and opportunities we face in converting genetic information into an improved understanding of the pathophysiology of epilepsy, and even more importantly, into new treatment approaches. We hope that the course and this supplement accomplished that goal, and communicated the tremendous excitement surrounding genetic research along with an appreciation for its ability to help patients with their disease and investigators with their research. We are particularly proud that speakers in the course came from five continents and included five women, illustrating the worldwide commitment of the epilepsy community to modern translational research for the benefit of patients. We welcome your comments.