ABSTRACT Atherothrombosis is a major global public health problem. Chronic atherosclerotic disease is often clinically silent and coexists across multiple vascular beds but, when complicated by thrombosis, it can result in an acute coronary syndrome, stroke, transient ischemic attack, and critical limb ischemia. Platelets play a role in the development of chronic atherosclerotic disease and are a key mediator of clinical events in atherothrombosis. Numerous clinical trials have tested antiplatelet agents for primary and secondary prevention, and several new antiplatelet drugs are under development. There is evidence of clear benefit of single and, in some cases, dual antiplatelet therapy in the prevention of recurrent cardiovascular and cerebrovascular complications. Dual antiplatelet therapy has emerged as the standard of care for acute coronary syndromes, with aspirin typically being used in combination with clopidogrel or one of the newer more potent ADP receptor antagonists (ticagrelor or prasugrel). Conversely, in chronic stable coronary disease, no benefit of dual antiplatelet therapy has yet been convincingly demonstrated Evidence supporting routine use of aspirin or any other antiplatelet agent for primary prevention is mixed, and this strategy should only be considered for individual high-risk patients in whom the thrombotic risk outweighs the risk of major bleeding complications.