The aim of this chapter is to delve comprehensively into ATP-sensitive potassium (KATP) channel, which is a ubiquitous class of potassium ion channels located in the biological membrane to sense intracellular nucleotide (ATP/ADP) concentration and mediate potassium efflux in various cell types (and mitochondria), thus functions as a link between intracellular metabolic state and cell membrane excitability. This chapter mainly includes five parts: the road to the discovery of KATP channel, protein subunit composition of KATP channel, the pharmacology of KATP channel, and the physiological and pathological roles of KATP channel, with particular emphasis on pancreas, heart, vascular smooth muscles, and the nervous system.