Liver failure in the neonatal period is challenging to diagnose and manage, and still carries a high mortality. With ongoing developments in the field of metabolic disorders and antiviral therapy, and the ability to offer liver transplantation to small babies, an overall survival of 40% has been achieved. Early recognition of liver failure, good supportive care and prompt referral to a paediatric liver transplant centre are essential elements in improving the outcome for these babies. Decisions about contra-indications to and timing of transplantation are complex as many of the disease processes are still evolving in the neonatal period, and extrahepatic disease, which cannot be corrected by a transplant, may appear later.