The adhesive protein von Willebrand factor contributes to platelet function by mediating the initiation and progression of thrombus formation at sites of vascular injury. In the last 2 years, there has been considerable progress in explaining the biologic properties of von Willebrand factor. The three-dimensional structure of specific domains has been explained, with the demonstration of distinct conformational changes in the A1 domain caused by single amino acid substitutions associated with enhanced binding to platelets. The structural and functional properties of the interaction between the von Willebrand factor A1 domain and glycoprotein Ibalpha have also been elucidated in greater detail, bringing researchers closer to understanding how this adhesive bond can oppose the fluid dynamic effects of rapidly flowing blood to initiate thrombus formation and, concurrently, contribute to platelet activation. Because hemodynamic forces greatly influence platelet responses to vascular injury in stenosed and partially occluded arteries, a detailed description of how von Willebrand factor interacts with tissues and platelets may help in the design of more specific therapeutic inhibitors of arterial thrombosis. Moreover, enlightening findings have been obtained on the link between regulation of von Willebrand factor multimer size and microvascular thrombosis. This progress in basic research has provided critical information to define with greater precision the role of von Willebrand factor in vascular biology and pathology.