Metabolic liver diseases encompass a wide range of entities which, due to a disorder of metabolism of a certain substance, deteriorate liver function. The most widespread entity of this group is the nonalcoholic fatty liver disease, with an incidence in constant rise, while some of the other entities are quite rare in the general population, such as familial amyloid polyneuropathy and primary hyperoxaluria type 1. The clinical manifestations of these diseases are highly variable and certain disorders manifest themselves already in the neonatal period, such as glycogen storage disease type 1a and primary hyperoxaluria type 1, whereas others, like Wilson's disease or alpha-1 antitrypsin deficiency, occur much later and are diagnosed long after the onset of the first symptoms, depending on the dominant symptomatology. In addition to functional abnormalities of the liver, the clinical manifestations may include a number of extrahepatic manifestations, such as pulmonary emphysema in A1AT deficiency, hyperpigmentations and diabetes in hereditary hemochromatosis, Kayser-Fleischer rings and neuropsychiatric symptoms in Wilson's disease, paresthesia and muscle weakness in familial amyloid polyneuropathy. This paper brings forth the challenges faced during the diagnosis and treatment of metabolic liver diseases in general, as well as a summary of the pathophysiological mechanisms and clinical presentation of these diseases.