Thromboembolic vascular diseases remain the main cause of death in Western industrialized societies. Anticoagulants retard the formation, growth, and embolization of thrombi and are effective agents in the prevention and treatment of thromboembolic disease. Anticoagulants in venous thromboembolism have been investigated extensively with rigorous randomized, controlled trials, while the roles for anticoagulants in arterial thromboembolism generally have evolved through natural history studies and empirical practice. Thus, many current guidelines for anticoagulant use in arterial disease are based on successful established routines and rational therapy. To effectively balance the efficacy and risks of anticoagulation, the vascular surgeon needs a thorough understanding of anticoagulant drugs, their mechanisms of action, and their proven and unproven indications. Since the first use of heparin in arterial surgery, a variety of new and different anticoagulants have become available, including low-molecular-weight heparins, heparin-like drugs, hirudins, and thrombin inhibitors. Despite their diverse actions, they all inhibit some portion of the plasma coagulation cascade, thus distinguishing them from platelet inhibitors or fibrinolytics. Every interference with the coagulation cascade carries a risk of minor, major, or fatal hemorrhage. To date, no drug or therapeutic strategy has succeeded fully in dissociating its antithrombotic effects from its risks of bleeding.