Achievement of infarct-related artery (IRA) patency with thrombolytic agents has improved the clinical outcome of patients with acute myocardial infarction (MI). Primary angioplasty (PTCA) for direct IRA reperfusion may further improve patient outcome by overcoming several limitations of thrombolytic therapy, e.g. by decreasing the risk of haemorrhagic stroke, increasing the achievement of brisk antegrade flow, decreasing the risk of IRA reocclusion, and allowing early identification of patients who need surgical revascularization. In the PAMI-1 randomized trial, primary PTCA was superior to thrombolytic therapy. The GUSTO-IIb angioplasty substudy supported the same conclusion but with a narrower margin of benefit from PTCA. In order to further improve the outcome of primary mechanical reperfusion, routine intra-aortic balloon pump (IABP) insertion in high-risk MI patients and primary stenting have been evaluated. In PAMI-2, there was no major clinical benefit in routine IABP insertion during primary PTCA in high-risk patients. In contrast, primary stenting appears to offer significant advantages over PTCA, especially by decreasing the need for subsequent IRA revascularization procedures as shown in the recent PAMI Stent Randomized Trial. Adjunctive pharmacotherapy with potent antiplatelet agents in acute MI is being evaluated both in combination with thrombolytic therapy, and with primary PTCA and stenting. Finally, meaningful consideration of cost-effectiveness and health policy guidelines is warranted to optimize the appropriate management of MI patients in the current era, given the increasingly complex and expensive therapeutic strategies available.