Atherosclerosis is considered an inflammatory disease. T-cells, macrophages, and mast cells infiltrate atherosclerotic plaques and platelets play an essential role releasing inflammatory mediators that stimulate plaque progression. This is important in acute coronary syndromes but it is also the mechanism involved in plaque progresion and endothelial dysfunction. Antiplatelet drugs exert their effects not only by inhibition of platelet aggregation but also through their antiinflammatory effect. Aspirin, thyenopiridines and GPIIb/IIIa inhibitors have antiinflammatory properties that involve different mechanisms of action, especially related to the blockade of platelet activation and platelet-leukocyte interactions. Testing platelet function in addition to assessing levels of inflammatory markers, and not only the risk of bleeding, could help in decision-making to balance the risk-benefit of anti-thrombotic treatment. Different clinical settings are associated with variable inflammatory states, and this could be, in part, responsible for variable response to treatment.