The platelet, a fascinating anucleate cell, is critically important for haemostasis. Platelet transfusions have greatly reduced the incidence of major haemorrhagic complications associated with the management of haematological and oncological disorders. However, some patients fail to receive the full benefit of platelet transfusions because they do not achieve the appropriate platelet count increment following transfusion. This review will discuss the aetiology, diagnosis, and management of refractoriness to platelet transfusion, a complicated problem for both the treating physicians and the transfusion services supporting these patients. Although advances have been made in the diagnosis and treatment of immune-mediated platelet refractoriness, which is usually caused by anti-human leucocyte antigen antibodies, non-immune causes, such as sepsis, remain problematic.