von Willebrand disease (VWD), caused by quantitative or qualitative abnormalities in von Willebrand factor (VWF) is considered the most common inherited bleeding disorder in humans. Mild and severe quantitative defects in VWF cause VWD types 1 and 3 respectively, whereas qualitative abnormalities induce VWD type 2. VWD has also been diagnosed in a number of animal species such as dogs, pigs, cats and horses, as a result of naturally occurring mutations. More recently, murine models have drawn a great deal of attention. Their small size along with their well-defined genetic background makes them ideal tools to study the in vivo function of VWF. The most commonly used model is the VWF-deficient mouse engineered through homologous recombination. However, models resulting from changes in modifier genes indirectly affecting VWF have also been described. These various models have proven very useful in elucidating some aspects of VWF biology not easily addressed through in vitro approaches.