The availability of platelet transfusions made possible intensive, myelosuppressive therapy. Chronic transfusion support is often complicated by refractoriness to platelet transfusions characterized by inadequate post-transfusion platelet count increments. Refractoriness is most commonly associated with a variety of clinical factors. Aggressive treatment of these clinical conditions often corrects the response to platelet transfusions. Fewer patients develop immune-mediated platelet destruction associated with alloantibodies to class I human leukocyte antigens (HLAs) and occasionally to platelet-specific antigens. The majority of these patients are successfully supported with HLA-matched or cross-match compatible single-donor platelet concentrates.