I nfarction is the most intensively studied medical intervention in the history of clinical investigation, with more than 200 000 patients enrolled in large scale, worldwide trials. The results of these trials have led to an irrevocably altered approach, with routine use of reperfusion treatment. Streptokinase, tissue plasminogen activator (t-PA), and new plasminogen activators have been shown to reduce mortality significantly, and the reduction is inversely proportional to the time that treatment is initiated from symptom onset. For patients treated in the first 60 minutes of symptom onset, the so called “golden hour”, mortality is reduced by more than 50%. Even frank prevention of the event can be assured in many patients treated in this very early time frame. Nevertheless, there are some major obstacles to optimal reperfusion treatment that have been increasingly recognised in recent years, which new directions in this field will hopefully circumvent. This paper will review the substantive progress in the field, including recognition of major pitfalls, and lay the groundwork for future improvements in pharmacologic myocardial reperfusion treatment. With the validation of intravenous thrombolytic treatment versus placebo in the classic GISSI 1 and ISIS 2 trials,1 2 the next step was to determine whether a higher level of early infarct vessel patency would result in improved survival. This was the focus of the GUSTO 1 trial which showed that a significant increase in patency at 90 minutes after treatment was initiated, from 30% with streptokinase to 54% with accelerated t-PA, was associated with a 15% reduction in mortality (fig 1).3 The term “patency” refers to brisk flow and clearance of angiographic contrast dye through the affected epicardial artery. Figure 1 (A) Mortality curves in GUSTO 1 by thrombolytic strategy assignment. For streptokinase (SK) the parentheses indicate the heparin strategy, intravenous (iv) or subcutaneous (sc). (B) …