Neonatal thrombocytopenia is a common clinical problem. The majority of episodes are early-onset thrombocytopenias due to impaired fetal megakaryocytopoiesis associated with placental insufficiency; the commonest causes of severe early-onset thrombocytopenia are immune thrombocytopenias, congenital infections, and asphyxia. By contrast, about 90% of cases of severe thrombocytopenia presenting after the first few days of life are due to late-onset bacterial sepsis, necrotizing enterocolitis, or both. Although clinically stable neonates tolerate relatively low platelet counts without significant risk of hemorrhage, ill or clinically unstable neonates with profound thrombocytopenia often have a poor outcome. Currently, the only therapy is platelet transfusion. Despite many published guidelines for platelet transfusion in the newborn, however, there have been no randomized trials to define the safe lower limit for platelet counts in sick neonates. The platelet threshold at which the benefits of transfusion outweigh the risks in neonates remains unclear. Well-designed trials are urgently needed.