Sudden unexpected death in epilepsy (SUDEP) is the most common cause of seizure-related death in children and adults with epilepsy. The incidence of SUDEP varies markedly by epilepsy severity, with increased rates in treatment resistant epilepsy, and in specific epilepsy syndromes, such as Dravet syndrome. Approaches to SUDEP prevention include improved seizure control, identification of seizure risk, and improved mechanism-specific interventions that are the focus of intense research. Leading theories about the mechanism of SUDEP include seizures, cardiac arrhythmias and arrest, respiratory insufficiency, central or cerebral “shutdown”, autonomic nervous system dysfunction, serotonin, genetic mutations, and combinations of these. Numerous preclinical models have been developed to identify specific mechanisms. This activity will include a review of the evidence regarding interventions demonstrated to review SUDEP risk as well as cutting-edge research exploring 3 specific mechanisms: the role of serotonin, postictal hypoxia, spreading brainstem depolarization and potential genes.