Recent application of genetic analysis to rare, hereditary epilepsies has resulted in the identification of mutations in genes encoding ion channels or functionally related proteins in several human and animal syndromes. Reviewed here are selected human and murine epilepsies that result from ion channel mutations. In humans, three autosomal-dominant disorders--benign familial neonatal convulsions, nocturnal frontal lobe epilepsy, and "generalized epilepsy with febrile seizures plus"--result from mutations affecting voltage-sensitive potassium channels, a central nicotinic acetylcholine receptor, and a voltage-sensitive sodium channel, respectively. In mice, four genetically distinct, autosomal-recessive models of absence epilepsy are caused by mutations in genes encoding three types of calcium channel subunits and a sodium-hydrogen ion exchanger. These findings suggest that variation in genes encoding ion channels could determine susceptibility to common human epilepsies.