Platelets play a crucial role in the physiology of the primary hemostasis and in the pathophysiological activity of arterial thrombosis, provide rapid protection against bleeding, and catalyze the formation of stable blood clots via the coagulation cascade. Over the past years, it has become clear that platelets are important, not only in hemostasis and thrombosis but also in inflammation and in distinct aspects of atherosclerosis. Nowadays, platelets are known to have a large variety of functions. Platelets are able to interact with a large variety of cell types, such as leukocytes, endothelial cells, and SMCs, and these interactions have been implicated in the pathophysiology of vascular inflammation. In addition, platelets carry a highly inflammatory payload and are able to transport, synthesize, and deposit cytokines, chemokines, and lipid mediators, thereby initiating and propagating atherosclerotic disease. In this review, the current state of the art of the proinflammatory functions in the context of atherosclerotic cardiovascular disease will be out-lined. J. Leukoc. Biol. 92: 1167-1175; 2012.