Each year, 1.1 million Americans suffer from MI and 700,000 Americans suffer from a new or recurrent stroke. These events are thrombotic in nature and therefore potentially both treatable and preventable with the appropriate use of antithrombotic agents. Current antithrombotic therapy targets three of four stages of thrombus formation including platelet activation, platelet aggregation, and coagulation cascade activation.There are no effective means to prevent the initial stage of platelet adhesion to injured arterial walls. This chapter reviews the mechanism of action, pharmacology and clinical use of agents for the prevention and treatment of arterial thrombosis. The current guidelines of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy are a valuable resource for anyone seeing cardiovascular patients and can be accessed online (www.chestjournal.org/content/vol126/3_suppl/).