Platelet-leukocyte interactions define a basic cell process that is characterized by the exchange of signals between platelets and different types of leukocytes and that bridges 2 fundamental pathophysiological events: atherothrombosis and inflammatory immune reactions. When this process takes place at the site of atherosclerotic plaque development or at the site of endothelial injury, platelet-dependent leukocyte recruitment and activation contributes to the inflammatory reaction of the vessel wall, which accounts for the exacerbation of atherosclerosis and for intimal hyperplasia and plaque instability. Moreover, platelet-leukocyte interactions may have a key role in modulating a wide array of responses of both the innate and adaptive immune systems, thus contributing to the pathogenesis of inflammatory diseases and tissue damage, as well as to host defense.