Potassium ion channels play critical roles in cell function, providing the maintenance of the membrane, repolarization of action potentials, and the regulation of firing frequency. Mutations in genes that interfere with K(v) ion channel function cause severe inherited diseases, such as episodic ataxia type 1, deafness, epilepsy, or cardiac arrhythmia. Because of their critical role in the central nervous system, all ion channels are targets for multiple pharmacologically active compounds. Better understanding of the structure and function of K(v) channels may eventually contribute to a more effective design of drugs. In this review, we show the recent data about domain organization of eukaryotic potassium voltage-gated ion channels. We are giving special attention to the interaction between the domains and the corresponding conformational changes upon activation of the channel.