Sudden unexpected death in epilepsy (SUDEP) is a significant cause of death for people with epilepsy. Recent research suggests that multiple factors may contribute and that both cardiac and respiratory mechanisms are involved. Both human and animal data suggest that specific genetic factors might play a role in some cases. Recent animal data suggest that serotonin might affect respiratory mechanisms and may be involved. Both cardiac and respiratory abnormalities are more likely with generalized tonic-clonic seizures. Uncontrolled epilepsy, particularly with generalized tonic-clonic seizures, appears to be the most highly associated modifiable risk factor for SUDEP.