Looking back at the last thirty years of studies on von Willebrand factor is a lesson on the importance of combining clinical observations with basic research. Most of what we know today originates from the perceptive evaluation of patients with congenital disorders of haemostasis such as haemophilia and von Willebrand disease. Understanding the causes of these diseases was akin to the current approach of using mutagenesis in animal models to get insights into the function of specific gene products. The information generated to date has been detailed and comprehensive, but looking into the future one sees that much remains to be done to understand how the role of von Willebrand factor and its primary platelet receptor, glycoprotein Ib, is integrated into the complex responses to vascular injury. Many challenges remain, along with the hope of translating the knowledge acquired into new and efficacious treatments for arterial thrombosis.