The healthy fetus has a platelet count of greater than 150 x 10(9)/L by the second trimester of pregnancy and only 2% of term infants are thrombocytopenic at birth. Severe thrombocytopenia (platelets < 50 x 10(9)/L) occurs in fewer than three per 1000 term infants, the most important cause being alloimmune thrombocytopenia. In contrast, in infants admitted to neonatal intensive care units, thrombocytopenia develops in 25% and in up to half of sick preterm infants. Recent evidence shows that these infants mostly have evidence of underlying impaired fetal megakaryocytopoiesis and platelet production following pregnancy complications characterized by placental insufficiency or fetal hypoxia. The mechanism of this is unknown. However, many neonatal complications exacerbate this thrombocytopenic potential and 20% of thrombocytopenias in neonatal intensive care unit patients are severe. Evidence-based guidelines for platelet transfusion therapy in these patients are yet to be defined, but as platelet underproduction underlies most neonatal thrombocytopenias, recombinant hemopoietic growth factors, including thrombopoietin and interkeukin-11, may be useful future therapies.