Episodic neurological phenotypes are a very interesting and important group of diseases affecting humans.These include disorders of skeletal and cardiac muscle, peripheral nerve, and brain.They range from episodic weakness syndromes to paroxysmal movement disorders that are quite rare.We have shown that ion channel gene mutations are responsible for many of these disorders but have also cloned novel genes causing epilepsy and parox ysmal dyskinesias that do not encode ion channels.One of these genes encodes a protein that we predict to function in stress response; this raises the possibility that proteins critical for homeostatic responses to altered membrane ex citability might be sights for genetic variants affecting risk for episodic disorders.More common episodic phenomena include cardiac arrhythmias, epilepsy syndromes, and headache.In rare Mendelian disorders, single gene muta tions are sufficient to cause dramatic phenotypes.Knowledge gained from molecular characterization of rare genetic disorders is informing studies of the genetically and clinically more complex diseases.Molecular characterization of all of these disorders is shedding light on pathophysiology and will ultimately lead to better diagnosis and treatment of patients.