Von Willebrand factor (VWF) is a blood glycoprotein that is required fornormal hemostasis, and deficiency of VWF, or von Willebrand disease (VWD), isthe most common inherited bleeding disorder. VWF mediates the adhesion ofplatelets to sites of vascular damage by binding to specific platelet membraneglycoproteins and to constituents of exposed connective tissue. Theseactivities appear to be regulated by allosteric mechanisms and possibly byhydrodynamic shear forces. VWF also is a carrier protein for blood clottingfactor VIII, and this interaction is required for normal factor VIII survivalin the circulation. VWF is assembled from identical ≈250 kDa subunits intodisulfide-linked multimers that may be >20,000 kDa. Mutations in VWD candisrupt this complex biosynthetic process at several steps to impair theassembly, intracellular targeting, or secretion of VWF multimers. Other VWDmutations impair the survival of VWF in plasma or the function of specificligand binding sites. This growing body of information about VWF synthesis,structure, and function has allowed the reclassification of VWD based upondistinct pathophysiologic mechanisms that appear to correlate with clincialsymptoms and the response to therapy.