Glycoprotein VI (GP6) is a 58kD platelet membrane glycoprotein that plays a crucial role in the collagen-induced activation and aggregation of platelets. It is uniquely expressed by cells of the megakaryocytic/platelet lineage, and is a member of the immunoglobulin gene superfamily, closely related to Fc receptor gamma chain (FcR?) and natural killer receptors. Glycoprotein VI plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant function may contribute to arterial and venous thrombus formation. The signaling pathway involves the FcR?, the Src kinases (likely Fyn/Lyn), the adapter protein LAT and leads to the activation of phospholipase C gamma2. GPVI deficiency can result in bleeding disorders. Further study should reveal the extent of GPVI involvement in thrombotic disease and allow the development of alternative anti-thrombotic compounds.