Achieving optimal outcomes in patients with acute coronary syndromes depends on early reperfusion supported by rapid initiation of adjunctive antiplatelet and anticoagulant therapy. The use of the ambulance setting to initiate treatment provides an opportunity to dramatically reduce the time between symptom onset and reperfusion, and a growing body of evidence shows that prehospital reperfusion therapy is associated with significantly better short-term and long-term outcomes than in-hospital administration of the same treatment. In patients with ST-segment elevation myocardial infarction, fibrinolysis must be supported by optimal antiplatelet therapy. Recent studies have shown that, compared with aspirin monotherapy, treatment with a combination of aspirin and clopidogrel significantly improves outcome. The majority of these patients should also receive heparin (unfractionated or low molecular weight). The experience of several European emergency response systems initiating prehospital treatment, shows that this strategy is highly effective in improving outcomes for patients with acute coronary syndromes.