Platelets play a crucial role in arterial thrombus formation as a final step of atherosclerosis. Atherosclerosis is initially triggered by dysfunctional endothelial cells via inflammatory processes. Recent studies demonstrate that platelets also play an important role in the initiation of atherosclerotic lesion by releasing inflammatory mediators. Thus, atherosclerosis and thrombosis are interdependent (atherothrombosis). As an initial step in thrombogenesis, platelets adhere to altered vascular surfaces or exposed subendothelial matrices. Following adhesion, they become activated, change shape, secrete granule contents, and aggregate to each other to form thrombi and provide a catalytic surface to enhance blood coagulation. A number of adhesive proteins [e.g. von Willebrand factor (VWF), collagen], cell-adhesion receptors (e.g. GPIb-IX, aIIbb3), and platelet receptors (e.g. P2Y12, GPVI, PAR1) are involved in thrombus formation. This review article describes molecular mechanisms for thrombus formation and the targets of newly developed anti-platelet agents.