Patients with refractory epilepsy face an elevated risk of sudden death, with rates as high as 1% per year. This phenomenon, known as sudden unexpected death in epilepsy (SUDEP), is believed to be a seizure-related occurrence, but the exact underlying mechanisms are uncertain. Both pulmonary and cardiac pathophysiologies have been proposed. The cardiac mechanism of greatest interest is the precipitation of arrhythmias by seizure discharges via the autonomic nervous system. SUDEP prevention has centered on effective seizure control, and epilepsy surgery has reduced SUDEP incidence in a number of studies. Additional prophylaxis methods are needed, however, for the large number of patients with treatment-refractory epilepsy. Future research should aim to clarify whether the association between seizures and autonomic dysfunction and cardiac arrhythmias extends to a demonstrable cardiac mechanism for SUDEP.