Heart attacks, or acute myocardial infarctions (AMI), affect more than one million people in the US every year. The damage that occurs to the heart by AMI is often permanent and as a result, the morbidity and mortality rates of patients that experience AMIs continue to be high. Consequently, AMI patients are at significantly increased risks for future myocardial infarctions, decreased heart function, heart failure, and death [Heart and Stroke statistical update. In American Heart Association (2002) 4]. In this review, we discuss the events that lead to cardiac damage by AMI. Specifically, we discuss the current understanding of the role of ischemic damage vs. reperfusion damage, which is induced by the return of blood, oxygen, and nutrients to the organ. We also discuss the role of apoptosis and necrosis in cardiac damage, the means to protect the heart from damage by ischemia and reperfusion, and the role of protein kinase C in these processes.