Platelets are important mediators of thrombosis in both healthy and diseased vessels. When platelets become activated by various soluble agonists or by adhesion to subendothelium under high shear, they release adenosine-5-diphosphate that acts in a positive feedback mechanism on two different G-protein coupled receptors (P2Y 12, P2Y 1) on platelets. This released adenosine-5-diphosphate, acting through P2Y 12, is critical for sustained aggregation and stabilization of thrombi. P2Y 12 is the target of antithrombotic drugs (ticlopidine, clopidogrel), whereas the role of P2Y 1 in thrombosis remains to be fully established.