In 1969, H.H. Jasper, A.A. Ward, and A. Pope and the Public Health Service Advisory Committee on the Epilepsies of the National Institutes of Health published the first edition of Basic Mechanisms of the Epilepsies. The book was developed following a workshop held in Colorado Springs and an open symposium. Since then, basic and clinical researchers in epilepsy have gathered together about every 14 years to assess where epilepsy research has been, what it has accomplished, and where it should go. Each time a book was published. In a foreword written for the second edition of Basic Mechanisms of the Epilepsies, published in 1983, Jasper reminded us that the original and ultimate goal of the Public Health Service committee was to search for a “better understanding of the epilepsies and seek more rational methods of their prevention and treatment.” In 1999, the third edition was named in honor of H.H. Jasper. This fourth edition of Jasper’s Basic Mechanisms of the Epilepsies is based on a series of workshops held for four days at Yosemite National Park in March 2009. The book (1) synthesizes the role of interactions between neurons, synapses, and glia in the initiation, spread, and arrest of seizures; (2) examines the molecular, cellular, and network plasticity mechanisms that subserve excitability, seizure susceptibility, and ultimately epileptogenesis; (3) provides a framework for expanding the genome of rare Mendelian epilepsies and understanding the complex heredity responsible for common epilepsies; (4) explores cellular mechanisms of the two main groups of presently known Mendelian epilepsy genes, the ion channelopathies and developmental epilepsy genes; and (5) for the first time in the Jasper’s series describes the current efforts to translate the discoveries in epilepsy disease mechanisms into new therapeutic strategies. The editors were assisted in reviewing the chapters by an editorial advisory board consisting of Giuseppe Biagini, Amy Brooks-Kayal, Wolfgang Löscher, Helen Scharfman, Phil Schwartzkroin, John Swann, and Annamaria Vezzani.