Neonatal cholestasis is a serious condition which requires urgent further investigation. Delayed referral of cholestatic neonates, however, is still a significant problem. Every child presenting with jaundice beyond the age of 2 weeks should be evaluated with a fractionated bilirubin checked. In case of neonatal cholestasis, the first step should be the assessment of coagulation and urgent parenteral vitamin K administration in case of coagulopathy and the exclusion of life-threatening conditions or disorders requiring urgent specific treatment. Any child presenting with acholic stools should be referred to a paediatric hepatology unit in order to confirm or rule out biliary atresia, as prognosis after porto-enterostomy correlates with younger age at the time of surgery. Once these conditions have been excluded, a more individualised approach is used based on anamnestic, clinical and further diagnostic findings. Besides specific medical or surgical therapy for selected diseases, early supportive treatment aiming for optimal growth and development and prevention of complications is of uttermost importance.