Several aspects of thermoregulation play a role in epilepsy. Circuitries involved in thermoregulation are affected by seizures and epilepsy, hyperthermia may be both cause and result of seizures, and hypothermia may prevent or abort seizures. Autonomic manifestations of seizures including thermoregulatory disturbances are common in a variety of clinical epilepsy syndromes. Experimental hyperthermia has been studied extensively, predominantly to investigate febrile seizures of childhood. In particular prolonged or complex febrile seizures have been associated with the later development of epilepsy in adulthood and the pathophysiology of how febrile seizures cause epilepsy is of tremendous interest. Febrile seizures represent an opportunity to potentially intervene early in life in susceptible individuals and affect epileptogenesis. The pathophysiologic underpinnings of how hyperthermia induces seizures and how this in turn results in epilepsy are controversial, but likely involve multiple factors. Both glutamatergic and GABAergic neurotransmission is affected, and numerous mutations in genes encoding ion channels have been identified. Cytokines such as interleukin-1β have been implicated in febrile seizures as well as susceptibility to provoked seizures later in life. Hyperthermia is a common feature of generalized convulsive status epilepticus, but may also be seen with nonconvulsive seizures, indicating involvement of thermoregulatory centers.