Blood platelets play a key role in maintaining the integrity of the vascular system through their ability to arrest bleeding (haemostasis) and promote repair of injured blood vessels. Considerable progress has been made in the last few years in our understanding of the adhesion mechanisms utilized by platelets to adhere to sites of vascular injury. Studies have helped define the precise role of von Willebrand factor (vWf), and its platelet receptor, glycoprotein (GP) Ib/V/IX, in initiating platelet-vessel wall and platelet-platelet adhesion contacts. In addition to its adhesive role, recent studies have highlighted the importance of GPIb/V/IX in regulating the cytoskeleton of platelets. GPIb/V/IX not only maintains the normal cytoskeletal architecture of resting platelets but also induces cytoskeletal reorganization following engagement of vWf. Somewhat surprisingly, the physical link between GPIb/V/IX and the membrane skeleton does not appear necessary for GPIb/V/IX-induced cytoskeletal reorganization. In contrast, this linkage appears critical for GPIb/V/IX to maintain cell adhesion under high shear and also for the ability of the cytoskeleton to exert negative regulatory effects on the GPIb-vWf interaction. Thus a complex functional relationship appears to exist between GPIb/V/IX and the membrane skeleton that goes well beyond preserving the normal cytoskeletal architecture of resting platelets.