Even though primary angioplasty for STEMI has significantly improved survival when compared with thrombolysis, there is still room for improvement. In fact, despite restoration of optimal epicardial flow in the vast majority of patients, suboptimal myocardial reperfusion is observed in a relatively Large proportion of them. The aim of this article is to provide an update review of adjunctive antithrombotic therapy to primary angioplasty for STEMI. The Horizons trial has shown a significant reduction in mortality and major bleeding complications, when compared with glycoprotein (Gp) IIb-IIa inhibitors. Thus, bivatirudin may be considered in primary angioplasty as an alternative strategy to heparin + Gp IIb-IIa inhibitors, especially in patients at high risk for bleeding complications. However, despite the negative results of the FINESSE trial, large evidence has been observed in favour of early administration of Gp IIb-IIIa inhibitors that should still be considered the preferred strategy, especially in high.-risk patients and within the first hours from symptom onset. Non-responsiveness to aspirin and clopidogrel is relatively frequent. However, future trials are needed to evaluate whether its routine assessment and change in therapy (higher dosages or switch to other ADP) may improve clinical outcome. Even though not demonstrated yet, it is conceivable to get the greatest benefits from early administration of clopidogrel as well, which might be considered as part of a facilitation strategy, together with early administration of Gp IIb-IIIa inhibitors. Due to stronger and faster inhibition of platelet aggregation, further benefits might be expected by early administration of new oral ADP-antagonist. As a consequence of the very low mortality currently achieved by primary angioplasty, additional endpoints, such as infarct size and myocardial perfusion, may be considered to explore the benefits of adjunctive antithrombotic therapies in future randomized trials among patients undergoing mechanical revascularization for STEMI.