Human leucocyte antigen (HLA) sensitisation, including the formation of antibodies against HLA, can cause serious effects in patients receiving blood. Under certain circumstances, donor HLA antibodies in the blood product can trigger the patient's granulocytes to release mediators that cause transfusion-associated lung injury (TRALI), a serious complication of transfusion. The HLA systems of both donor and patient are involved in transfusion-associated graft-versus-host disease, which is a rare disease with a high mortality. Patient HLA antibodies can destroy incompatible platelets and may cause refractoriness to platelet transfusion. Identification of a patient's HLA antibody specificities is necessary for issuing compatible platelets to overcome refractoriness. Many techniques for the detection and identification of HLA antibodies have been developed, including complement-dependent cytotoxicity assay, bead-based assays, the platelet adhesion immunofluorescence test, and the monoclonal antibody-specific immobilisation of platelet antigens assay. Different strategies for the selection of HLA-compatible platelets are applied. These strategies depend on the breadth of antibody reactivity and range from avoiding single HLA antigens in the platelet concentrates issued to apheresis of platelets from HLA-identical donors. The mechanisms of HLA sensitisation and the efforts made to provide compatible blood products to sensitised patients are reviewed in this article from the perspective of clinical transfusion medicine.