BACKGROUND: Lack of adequate post-transfusion platelet count increments - platelet refractoriness - is a complication of chronic platelet support shown by 5-15% of chronic platelet recipients. INFORMATION SOURCES. To review the frequency, diagnosis, management and cost of platelet refractoriness, particularly as described in English literature published during 2000-2004 and searched with Pubmed. RESULTS: Refractoriness is usually defined as the occurrence of 2-3 post-transfusion platelet count increments, corrected for the patient's size and number of administered platelets, at 10-60 minutes and at 18-24 hours post-transfusion below 4,500-5,000 and 2,500 platelets per microliter respectively. In most cases refractoriness is associated with clinical and pharmacological causes. In those cases in which refractoriness is due to immune factors, anti-HLA antibodies are most frequently implicated. Validated strategies to select effective platelets for alloimmunized refractory patients include the selection of HLA-matched platelet donors from HLA-typed donor registries and the use of manual or automated platelet cross-matching. Both strategies, which require significant organizational and financial resources, can provide successful platelet support in about 2/3 of transfusions. INTERPRETATION AND CONCLUSIONS: Unlike the less frequent cause of platelet refractoriness (anti-HLA alloimmunization) whose detrimental effect can be overcome by using HLA compatible platelets, the main causes of platelet refractoriness (patient's poor clinical condition and the use of drugs affecting platelet survival and function) remain largely unresolved.