von Willebrand factor (VWF) is a long plasma protein that contains many domains and each domain has its own function. VWF exists in a multimeric form and performs varieties of functions in the human body, including thrombus formation and blood coagulation. The crystal structures of three subdomains are known, and, interestingly, all three domains share identical three-dimensional fold with α−β−α sandwiched model. VWF is directly associated with different types of von Willebrand disease. In this review, our aim is to gather recent developments on structure and functions of VWF and its clinical relevance.