Beyond their role in hemostasis and thrombosis platelets are critically involved in the onset of atherosclerosis. Platelets represent an important linkage between inflammation, and atherogenesis. Platelets interact with inflammatory cells including leukocytes and endothelium. These interactions lead to leukocyte recruitment towards the vascular wall, initiating extravasation of circulating mononuclear cells and foam cell generation. Inflammatory processes within the arterial wall result in development of atherosclerotic lesions and atheroprogression. Inhibition of platelet interaction with the arterial wall results in attenuation of atherosclerosis and may be a novel therapeutic strategy in treatment of high-risk patients.