Von Willebrand factor (vWF) is a blood multimeric glycoprotein present in blood plasma and produced constitutively as ultra-large vWF in endothelium (in the Weibel-Palade bodies), megakaryocytes (α-granules of platelets), and subendothelial connective tissue. Multimers of vWF can be extremely large, >20,000 kDa, and consist of over 80 subunits of 250 kDa each. Every monomer of vWF contains a number of specific domains with a specific function, elements of note are D’/D3 domain, A1 domain, A3 domain, C1 domain and the “cysteine knot” domain. The primary function of vWF is binding to other proteins, in particular factor VIII, and it is important in platelet adhesion to wound sites. vWF plays a major role in blood coagulation. Therefore, vWF deficiency or dysfunction (von Willebrand disease) leads to a bleeding tendency, which is most apparent in tissues having high blood flow shear in narrow vessels. Monitoring of vWF levels in serum provides more detailed insights in several pathological situations such as thrombotic thrombocytopenic purpura, Heyde’s syndrome, and possibly hemolytic-uremic syndrome.