Potassium channels regulate the influx and efflux of K+ ions in various cell types that generate and propagate action potential associated with excitation, contraction and relaxation of various cell types. Although redox active cysteines are critically important for channel activity, redox regulation of K+ channels by thioredoxin has not been systematically reviewed. Redox regulation of K+ channel is now increasingly recognized as drug targets in pathological condition of several cardiovascular disease processes. The role of thioredoxin in regulation of these channels and its implication in pathological conditions have not been adequately reviewed. This review specifically focuses on the redox-regulatory role of thioredoxin on K+ channel structure and function in physiological and pathophysiological conditions. Ion channels including K+ channel have been implicated in the functioning of cardiomyocyte excitation-contraction coupling, vascular hyperpolarization, cellular proliferation, and neuronal stimulation in physiological and pathophysiological conditions. Although, oxidation-reduction of ion channels is critically important in their function, role of thioredoxin, redox regulatory protein in regulation of these channels and its implication in pathological conditions need to be studied to gain further insight into channel function. Future studies need to map all redox regulatory pathways in channel structure and function using novel mouse models, redox proteomic and signal transduction studies, which modulate various currents and altered excitability of relevant cells implicated in a pathological condition. We are yet at infancy of studies related to redox control of various K+ channels and structured and focused studies with novel animal models.