The development of “next-generation” or massively parallel sequencing (MPS) has had the greatest impact on gene discovery. Massively parallel sequencing facilitates rapid and cost-effective sequence analysis of multiple genes simultaneously, and since its introduction, there has been an explosion of gene discovery in the DEEs.2 Common approaches that employ MPS are targeted sequencing, in which multiple genes (ranging from dozens to hundreds) are sequenced simultaneously, and exome sequencing, a more comprehensive and unbiased approach in which all ∼20 000 human genes are sequenced. Notably, the same approaches applied in the research setting for gene discovery moved rapidly into clinical laboratories for diagnosis, and today, there are dozens of tests available that test a few to hundreds of epilepsy-related genes simultaneously (gene panels) as well as clinical exome sequencing.