The hemostatic mechanism is a critical component of a normally functioning circulatory system, preventing life-threatening hemorrhage and assisting in the maintenance of vascular integrity. For longer than half a century, however, nonphysiological intravascular coagulation and thrombosis have been recognized as playing central roles in cardiovascular morbidity and mortality. In order to provide a conceptual framework for the use of antithrombotic therapy, the pathogenetic mechanisms underlying thrombotic events must be clearly understood. The purpose of this review is to define these mechanisms, and discuss the use of anticoagulants in both the prevention and treatment of cardiovascular diseases.