Platelets are central to the pathophysiology of an array of vascular disorders. Current platelet-inhibitor drugs reduce platelet aggregation through one of three pathways but do not prevent initial platelet adhesion. The most extensive clinical experience is with aspirin, an irreversible inhibitor of cyclooxygenase. Aspirin is clinically effective and has few gastrointestinal side effects if used at a dosage of 150 to 300 mg per day. Large clinical trials have documented the benefits of aspirin in arterial thromboembolic disease. It is effective in the primary and secondary prevention of myocardial infarction, including patients with unstable angina; reduces the acute thrombotic complications of coronary angioplasty and revascularization surgery; and also reduces cerebral ischemic events in patients with cerebrovascular disease. Aspirin is less effective for thrombi arising from the venous system or intracardiac chambers, which respond well to anticoagulants. Dipyridamole and sulfinpyrazone are most effective at preventing thrombosis on prosthetic surfaces. Dipyridamole reduces emboli from mechanical prosthetic valves when combined with warfarin and, unlike aspirin plus warfarin, does not increase bleeding complications. Newer agents such as ticlopidine and the thrombin inhibitor, hirudin, appear promising but require further evaluation. Because thrombin plays a critical role in mechanisms of arterial thrombosis, its inhibition appears promising for future therapy.