Platelets are essential for the maintenance of vascular integrity and control of bleeding at sites of injury, but they are also implicated in the progression of atherosclerotic lesions and arterial vascular thrombosis. The use of antiplatelet drugs for the primary and secondary prevention of cardiovascular and cerebrovascular thromboses in adult populations has been extensively evaluated, resulting in defined management strategies. Much less is known about the appropriate use of antiplatelet drugs (primarily aspirin) in infants and children for secondary prevention in ischemic stroke, for prevention of coronary artery thrombosis in Kawasaki disease, or for prevention of thromboembolism following surgery for congenital cardiac disease. Additional studies will be required to evaluate the relative benefits of aspirin and anticoagulants in these settings. A role for newer antiplatelet drugs in the management of pediatric arterial thrombosis is as yet unexplored.