The most critical determinant of prognosis in patients with acute myocardial infarction (MI) is infarct magnitude, which can be established within several hours of an attack. The importance of the subsequent healing process is not negligible, however. In fact, much experimental and clinical evidence suggests that late reperfusion of the infarct-related coronary artery--i.e. at times too late to salvage the myocardium within the area at risk-is beneficial for reducing left ventricular remodelling and decreasing mortality ('open artery hypothesis'). For instance, one recent study highlighted the beneficial effects of late reperfusion therapy on the infarct tissue cell dynamics following acute MI. Nonetheless, several recent large, randomized clinical trials have failed to provide evidence of such benefits, refuting the clinical efficacy of late reperfusion. In addition, they also underscore the need for revised clinical studies in which there is less heterogeneity in the timing of reperfusion and in the initial infarct size, as well as the need for sustained patency of the recanalized artery. This review focuses on the effects of late reperfusion on the pathophysiology of MI in the context of the infarct tissue dynamics and clinical outcomes. We also discuss the issues that need to be resolved to improve clinical application.