Potassium (K(+)) channels are encoded by approximately 80 genes in mammals. They are expressed in many tissues and have diverse physiological roles. Human K(+) channels are divided mainly into calcium (Ca(2+))-activated (K(Ca)), inward-rectifying (K(IR)), two-pore (K(2P)), and voltage-gated (K(v)) channels. The K(v) channels form the largest family, with approximately 40 genes. Owing to their involvement in many diseases and their specific expression patterns and physiological roles, K(+) channels present an attractive target for the development of new therapies. This review summarizes the physiological and pathophysiological roles of various potassium channels with respect to their therapeutic potential for disorders with a disturbed neuronal excitability such as epilepsy, migraine, neuropathic pain, or stroke.