The present review firstly gives some details regarding nosological approach to the cholestatic syndrome. In addition, different steps are considered, identifying 12 possible metabolic defects responsible for determining a cholestatic syndrome either in man or in experimental conditions. Eleven defects out of these 12 steps should be considered related to the structure and function of the hepatocyte, whereas the twelfth one, which comprises 3 different sub-groups, is based on a mechanical obstructive mechanism, localized exclusively into the liver parenchyma, thus resembling the other ones included in the chapter of intrahepatic cholestasis.