Long-term follow-up of placebo-controlled thrombolysis trials has proven that the survival benefit from thrombolysis in acute myocardial infarction (AMI) is maintained for up to 10 years. Ongoing research is being conducted with the aim to further improve early restoration of blood flow in the infarct vessel and, thus, reperfusion of the infarcted myocardium in patients with AMI, with the ultimate goal to improve survival. In two recent mega-trials, two new single-bolus fibrinolytics (lanoteplase and TNK-tissue plasminogen activator) were shown to be equivalent to front-loaded alteplase in reducing infarct mortality. The ease of application of these agents might help reduce the time from symptom onset to start of therapy. More potent thrombin inhibitors such as hirudin and hirulog seem to speed up thrombolysis with streptokinase and reduce the rate of reinfarctions. Very promising results are derived from angiographic trials combining reduced doses of thrombolytics with glycoprotein IIb/IIIa inhibitors. Advances in mechanical revascularization can be achieved with the use of stents and better conjunctive therapies. All of these developments are expected to further improve clinical outcome of patients with AMI in the near future.