Advances in genetic analysis are fundamentally changing our understanding of the causes of epilepsy, and promise to add more precision to diagnosis and management of the clinical disorder. Single gene mutations that appear among more complex patterns of genomic variation can now be readily defined. As each mutation is identified, its predicted effects can now be validated in neurons derived from the patient’s own stem cells, allowing a more precise understanding of the cellular defect. Parallel breakthroughs in genetic engineering now allow the creation of developmental experimental models bearing mutations identical to the human disorder. These models enable investigators to carry out detailed exploration of the downstream effects of the defective gene on the developing nervous system, and a framework for pursuing new therapeutic target discovery. Once these genetic strategies are combined with interdisciplinary technological advances in bioinformatics, imaging, and drug development, the promise of delivering clinical cures for some genetic epilepsies will be within our reach.