ATP-sensitive potassium channels allow for the coupling of membrane potential to cellular metabolic status. Two K(ATP) channel subtypes coexist in the myocardium with one subtype located in the sarcolemma membrane and the other in the inner membrane of the mitochondria. The ATP-sensitive potassium channels can be pharmacologically modulated by a family of structurally diverse agents of varied potency and selectivity, collectively known as potassium channel openers and blockers. Sufficient evidence exists to indicate that the ATP-sensitive potassium channels and in particular the mitochondrial ATP-sensitive potassium channels play an important role both as a trigger and an effector in surgical cardioprotection. In this review, the biochemistry and specificity of the ATP-sensitive potassium channels is examined in relation to surgical cardioprotection.