Although von Willebrand disease (VWD) has a very long history, our understanding and treatment of the bleeding disorder has only evolved during the past 50 years or so. It was not until the 1920s that VWD was first recognized as a disease separate from that of classical haemophilia. It then took another 30 years before the first effective treatment was developed. Since then, the medical management of VWD has evolved considerably, but not without its ups and downs. One of the key milestones in the evolution of the treatment of VWD was the development of Haemate P/Humate-P (CSL Behring) - the first virus-inactivated factor VIII plasma product. For 25 years, this concentrate has demonstrated excellent clinical efficacy and safety for patients with VWD and for those with haemophilia. This article provides an historical overview of the early landmark efforts to ensure a safe plasma-derived replacement product and outlines the clinical evolution in the use of Haemate P.