Atherosclerosis is a progressive and generalized disease whose ultimate complication is atherothrombosis. Atherosclerotic plaque formation stands at the crossroads of multiple systems including lipid metabolism, endothelial dysfunction, immunity, inflammation, hemostasis, angiogenesis, and tissue repair. The mainstay of prevention includes risk factor management through lifestyle modification and treatment of underlying disease. Blood platelets and the coagulation system play a central role, both in acute thrombosis following plaque rupture, and in vascular inflammation and atherosclerotic plaque formation. Management of the acute phase of thrombosis includes inhibition of platelet function by aspirin and P2Y12 receptor and GP-IIbIIIa inhibitors, in combination with anticoagulants; secondary prevention is based on antiplatelet therapy. New vascular and platelet targets promise major strides in terms of antiatherothrombotic strategies...