INTRODUCTION: Within the last decade, next-generation sequencing (NGS) has resulted in remarkable advances in the field of epilepsy genetics. NGS has become a routine part of the diagnostic workup in many countries. A workup that has led to higher diagnostic yields and insights into the underlying disease mechanisms. Areas covered: In this review, we report on the recent contributions of NGS testing to the diagnosis and the understanding of pathophysiological mechanisms, phenotypic variability, and genetic heterogeneity of different epilepsies including developmental and/or epileptic encephalopathies, focal and generalized epilepsies. Furthermore, we discuss how the increased knowledge of the genetic architecture of the epilepsies can be translated into more personalized treatment. Expert opinion/commentary: Targeted gene panels or whole exome sequencing can provide a genetic diagnosis for up to 30% of the patients with early-onset epilepsy. Despite current technical limitations, NGS-based technologies can become the new first-tier diagnostic tests in the epilepsies. As the pool of genetically diagnosed patients has increased, so has the demand for more accurate treatment. Approximately 25% of the epilepsy patients with de novo mutations have genetic diagnoses with potential targets for precision medicine approaches, thus illustrating the enormous utility of genetic testing for therapeutic decision-making.