Several studies suggest an important role for platelets in atherogenesis, not only as mediators of thrombus formation, but also as inducers of inflammation. Several lines of evidence indicate that platelets are potent inflammatory cells that induce inflammatory responses in adjacent cells such as leukocytes and endothelial cells. Platelets may also themselves respond to inflammatory mediators produced by these neighboring cells. These platelet-mediated inflammatory pathways contribute to atherogenesis in both the early and late stage of the process. The bidirectional interaction between platelets and other cells may also be involved in the nonresolving inflammation characterizing atherosclerosis. In patients with atherosclerotic disorders, platelet-mediated inflammation appears to be operating in spite of the wide use of platelet-inhibiting drugs. This underscores the need for new therapeutic tools that more specifically target the pathways in platelet-mediated inflammation.