Anticoagulation has proven to be a key component in the management of acute coronary syndromes (ACS). Pharmacological agents with various modes of action are utilized to reduce thrombus development by impairing thrombin formation, platelet activation, and platelet aggregation. The optimal management of these patients is to achieve maximal anti-ischemic benefit while avoiding bleeding complications. Synthetic "novel" agents have been developed to specifically target factor Xa or thrombin to achieve this goal. A growing amount of data show that these agents provide a net clinical benefit in the setting of stable ischemic heart disease, unstable angina, non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI).