Platelet-dependent thrombus formation is a key event in the pathogenesis of acute myocardial infarction (AMI). Platelets mediate both thrombotic occlusion of the entire epicardial coronary artery and also accumulate in the microcirculation resulting in impairment of microcirculation and provoking myocardial ischemia during reperfusion. In the past, our understanding of platelet function in myocardial infarction (MI) and reperfusion has extended substantially resulting in development of novel and clinically effective treatment strategies. This review summarizes the mechanisms of coronary thrombosis and consequences of platelet accumulation in reperfused myocardium. Basic pathophysiological mechanisms of platelet adhesion and secretion are reviewed first, followed by the description of the molecular steps involved in platelet-mediated thrombus formation around an atherosclerotic plaque. Next, the role of platelets in inflammation is summarized with the focus on platelet–endothelium and platelet–leukocyte interactions.