Ischemic heart disease is one of the most prevalent diseases with a high impact on mortality and morbidity. The main process implicated in acute coronary syndromes (ACS) including its most severe form, the ST elevation myocardial infarction (STEMI), is the development of thrombosis subsequently of plaque erodation or rupture. The thrombus is formed by aggregates of platelets that furthermore drive the process of coagulation, that in this turn stimulates platelet aderation and aggregation, causing a vicious circle. From these physiopathological mechanism derive the indication and role of antiplatelets and anticoagulation in STEMI. Antiplatelets and anticoagulants play a central role in the therapeutic management of STEMI along with the interventional therapy. Correctly conducted by all physicians involved in the management of patients with STEMI, it reduces the area of ischemia, as well as mortality and other major adverse cardiovascular events. The following article will review the antithrombotic treatment adjuvant to the interventional treatment and the evidence based indications for treatment in STEMI.