Infarction 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.