Neonatal jaundice persisting beyond 14 days of age is a common clinical scenario. The vast majority of affected children have a benign unconjugated hyperbilirubinemia, but included in this clinical presentation is a group of neonates with conjugated hyperbilirubinemia and liver disease. Early identification of liver disease improves the infant's outcome, especially for those with extrahepatic biliary atresia. The present paper reviews the approach to the neonate with prolonged jaundice, including clinical presentation, when to proceed with initial investigations, timing of referral, further investigations and management, and provides an overview of the more common causes of neonatal cholestatic liver disease.