The heterogeneous nature of the diseases causing neonatal cholestasis, and the wide range of overlap among the specific entity frequently create serious challenges in their diagnosis. Moreover, the spectrum of correlated nutritional abnormalities in children with chronic cholestasis dictates a complex approach to their management. Nevertheless, pediatricians should be aware of the importance to recognize rapidly a specific treatable metabolic, infectious or malformative disease, in order to institute an early, specific, and effective treatment. However, despite all the still unanswered questions, in the last few years a tremendous progress has been achieved in the development of instruments and clinical procedures for diagnosis and therapy. Moreover, since orthotopic liver transplantation has been accepted as the treatment of choice of end-stage disease, a great deal of interest has been focused on the modalities of intervention applicable during progression of the disease. In this regard, nutritional support plays an increasing important role, since improved growth of these infants has a direct impact on their survival and suitability as candidates for liver transplant surgery. In the present article, Authors make an up-to-date of the main problems correlated with the diagnosis and management of chronic cholestasis.