Platelet activation and thrombin formation are integral in the pathophysiology of acute coronary syndrome. Currently available pharmacotherapies inhibit the cascade of platelet aggregation and activation, and prevent thrombin formation to limit platelet-fibrin complex formation, thus maintaining coronary patency and ultimately improving clinical outcomes. This is a rapidly evolving field with next-generation antithrombotic combinations aimed at achieving the "Holy Grail" of improved anti-ischemic efficacy whilst minimizing bleeding risk. Our review article focuses on the use of antithrombotic agents for the contemporary management of patients with ACS.