This article highlights studies in three major domains of potential mechanisms of sudden unexplained death in epilepsy (SUDEP): cardiac, respiratory, and autonomic. Ictal cardiac arrest is a clinically rare but well‐recognized potential mechanism of SUDEP. Studies have failed to identify preexisting cardiac electrophysiologic or structural abnormalities that distinguish SUDEP persons. Some degree of pulmonary congestion is a common autopsy finding, but severe pulmonary edema occurs very rarely with seizures. In contrast, periictal apnea and hypoxia occur commonly with generalized tonic–clonic seizures and, to a lesser degree, with complex partial seizures. There are several animal models of postictal respiratory arrest. Postictal respiratory arrest in audiogenic seizure mice can be induced by serotonin receptor inhibition or prevented by selective serotonin reuptake inhibitor (SSRI) drugs. Reduced heart rate variability occurs in patients with refractory epilepsy and can be induced in animal seizure models, but its precise role in predisposing persons to sudden death requires further investigation.