Although neonatal thrombocytopenia (platelet count < 150 × 109/l) is a common finding in hospital practice, a careful clinical history and examination of the blood film is often sufficient to establish the diagnosis and guide management without the need for further investigations. In preterm neonates, early-onset thrombocytopenia (<72 h) is usually secondary to antenatal causes, has a characteristic pattern and resolves without complications or the need for treatment. By contrast, late-onset thrombocytopenia in preterm neonates (>72 h) is nearly always due to post-natally acquired bacterial infection and/or necrotizing enterocolitis, which rapidly leads to severe thrombocytopenia (platelet count < 50 × 109/l). Thrombocytopenia is much less common in term neonates and the most important cause is neonatal alloimmune thrombocytopenia (NAIT), which confers a high risk of perinatal intracranial haemorrhage and long-term neurological disability. Prompt diagnosis and transfusion of human platelet antigen-compatible platelets is key to the successful management of NAIT. Recent studies suggest that more than half of neonates with severe thrombocytopenia receive platelet transfusion(s) based on consensus national or local guidelines despite little evidence of benefit. The most pressing problem in management of neonatal thrombocytopenia is identification of safe, effective platelet transfusion therapy and controlled trials are urgently needed.