Recent data from a number of independent laboratories have implicated ionic disturbances within the myocardium as being a critical contributory factor in injury to the heart during ischemia/reperfusion. The present treatise discusses the data supporting a role for Ca2+, Na+ and K+ in ischemic/reperfusion injury. The mechanism whereby intracellular ionic homeostasis becomes altered is the focus of the review. In particular, the evidence in support of an involvement of abnormal ion movements through Na+/H+ exchange, Na+ channels and the ATP-sensitive K+ channel in ischemic/reperfusion injury is advanced.