Even though for certain varieties of neonatal thrombocytopenia, intravenous immunoglobulin or corticosteroids are recommended as treatments, platelet transfusions represent the only specific therapy currently available for most thrombocytopenic neonates in NICUs. The majority of these NICU platelet transfusions, up to 98% in some recent reports, are given to prevent, rather than to treat, bleeding. The trigger limit of platelet count to prophylactically treat non-bleeding patients is generally arbitrary. A complete definition, of the benefits and the risks of prophylactic platelet transfusions in thrombocytopenic neonates is necessary. In fact, there is great variability worldwide in neonatal platelet transfusion practice, due to the lack of concrete evidence to guide transfusion decisions. Evidence-based guidelines do not exist to decide when platelet transfusion should be given. The practice of neonatal platelet transfusions is based almost entirely on expert opinion and reasoning. Consequently, these practices, not supported by definitive data, vary widely. To increase benefits and safety, new widespread changes in platelet transfusion guidelines are necessary. New transfusion paradigms should not be based on reasoning alone, but on important experimental validation. The neonatologists would better accept them and more closely adhere to.