Acquired von Willebrand disease (AVWD) is a heterogeneous, life‐threatening and bleeding disorder, usually associated with underlying disorders ranging from lympho‐ and myeloproliferative disorders to certain type of solid tumours, autoimmune diseases, cardiovascular disorders and drug therapies. AVWD is a complex multicausal disorder that is very often underdiagnosed or misdiagnosed. AVWD is usually characterised by a negative personal or family bleeding history and a late onset, even if it has to be considered in childhood. It is characterised by several different pathogenetic mechanisms, but all of them cause low circulating levels of von Willebrand factor (VWF), even if normally synthesised and released. VWF plays an important role in haemostasis, participating actively in platelet–subendothelium and platelet‐to‐platelet adhesion, promoting platelet aggregation and is a carrier protein for coagulation factor VIII. No simple, single laboratory test is available to screen for AVWD, and this makes it very challenging for clinicians to diagnose and treat the disorder. AVWD diagnosis requires a very experienced laboratory and is made using several specific laboratory tests. Key Concepts Primary haemostasis: pivotal role of von Willebrand factor (VWF) in platelet aggregation and adhesion. VWF protein's quaternary structure and its functional role. Congenital or acquired VWF deficiency. Acquired von Willebrand disease (AVWD) is a bleeding disorder characterised by mucocutaneous bleeding; although AVWD has, generally, a mild clinical impact, it must be seriously considered in some medical conditions. Role of autoantibodies and metalloproteases in AVWD. Clinical chemistry laboratory tests have an important function in the diagnosis of AVWD. Desmopressin achieves the main treatment goals of AVWD, such as control acute bleeding and prevent bleeding in high‐risk situations.