Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in adults and in the pediatric population of the western world; in a substantial proportion of subjects it takes on the characteristics of non-alcoholic steatohepatitis (NASH). The clinical significance of NAFLD is motivated by epidemiological data and its impact on liver-related morbidity and mortality on one hand and on the cardiovascular one on the other. The presence and extent of fibrosis on liver biopsy is the most relevant feature in predicting liver mortality, but the concept that the "simple steatosis" is benign has been recently questioned, especially in the presence of type 2 diabetes. Because the diagnosis of NASH is made by liver biopsy, the efforts of the scientific community are currently oriented to the search of non-invasive biomarkers of liver injury applicable on a large scale and of genetic polymorphisms associated to NASH in order to properly address the screening programs, follow-up and therapeutic attempts. Next to the therapy directed to the treatment of concomitant metabolic disorders, new drugs are being evaluated in clinical trials having as target the histologic resolution of NASH and regression of fibrosis.