Thrombocytopenia remains a common problem in sick newborns. A quarter of all neonates admitted to neonatal intensive care units develop thrombocytopenia, and in 20% of episodes the thrombocytopenia is severe (platelets <50 × 109/L). Practical and clinically relevant classifications of neonatal thrombocytopenia have now been developed which, by highlighting the principal conditions precipitating severe thrombocytopenia (eg, sepsis, necrotizing enterocolitis, perinatal asphyxia, and the immune thrombocytopenias), aid the practicing neonatologist. Recent reviews demonstrate that many neonates with severe thrombocytopenia receive repeated platelet transfusions, although evidence of their clinical benefit is lacking, and there exists a significant variation in platelet transfusion practice between centers. These facts support the need for the development of evidence-based protocols for platelet transfusion in the newborn and stimulate continued interest in the potential of hemopoietic growth factors (eg, thrombopoietin and interleukin-11) to prevent or treat neonatal thrombocytopenia.