The frequency of platelet-specific antibodies in multitransfused patients and their implication in platelet transfusion refractoriness has been a matter of controversy for years. The main reasons are the difficulties encountered in differentiating between HLA- and platelet-specific antibodies and, within platelet-specific antibodies, between auto- or alloantibodies, using the available platelet antiglobulin test. In the recent years, capture assays were developed, using immobilized platelet membrane glycoprotein (GP) carrying the antigens under investigation to avoid using whole platelets. These assays overcome the difficulties in differentiating platelet-reactive antibody mixtures and allow determination of antibody specificity. For the group of highly HLA-immunized patients in need for HLA-matched single donor platelets, however, there are only as many as 25% will have additional platelet-specific alloantibodies. These platelet-specific alloantibodies will prohibit satisfactory transfusion results if HLA-matched but HPA-incompatible platelets are transfused.