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Platelets exhibit a major role in development and progression of atherothrombosis. The normal function of platelets is to secure hemostasis at sites of vascular injuries. Abnormal endovascular structure may result in excessive platelet function with consequence of progressive or acute reduction in vascular lumen and cessation of blood flow. Despite succeeding in averting bleeding, total occlusion of a vessel leads to inevitable ischemia with eventual cell death upon lack of blood supply clinically manifesting as myocardial infarction in coronary vessels, cerebral infarction (stroke) in cerebral vessels, or peripheral gangrene in peripheral arterial disease. Antiplatelets long have been used to halt the process of atherothrombosis preventing further tissue damage at the expense of bleeding as well as other side effects. In this review, the role of antiplatelets in primary and secondary prevention of thrombotic events is explored in light of evidence based clinical practice.