The treatment and therapy of acute myocardial infarction has substantially improved during the past decades. After thrombotic coronary occlusion had been identified as the underlying cause of myocardial infarction, thrombolysis emerged as the standard therapy. The development of more and more effective thrombolytic therapies and optimization of adjunctive antithrombotic therapies resulted in improved clinical outcomes and decreased mortality rates of acute myocardial infarction patients. Optimization of percutaneous coronary intervention (PCI) techniques including implantation of coronary stents shifted the therapeutic approach from thrombolysis toward acute mechanical reperfusion. The safety and efficacy profile of PCI has been made possible by the development of potent antiplatelet agents such as clopidogrel and glycoprotein (GP) IIb/IIIa antagonists. For the future therapy of acute myocardial infarction the following goals will be important to consider: (1) are there ways to increase the percentage of patients reaching out for medical support when suffering from acute myocardial infarction?, (2) what strategies will be useful to shorten coronary reperfusion time?, (3) are there means to protect affected myocardium from ischemic damage?, and (4) can necrotic myocardium be reconstituted functionally? Potential approaches such as improved public information, combination of thrombolytic and interventional therapy to accelerate coronary reperfusion, pharmacological protection of myocardium by modulation of myocardial metabolism or protection from reperfusion damage as well as progenitor cell therapy are discussed in this overview.