Obesity is a major risk factor for malign and non-malign diseases of the gastrointestinal tract. Non-alcoholic fatty liver disease (NAFLD) is an outstanding example for the complex pathophysiology of the metabolic system and represents both source and consequence of the metabolic syndrome. NAFLD has a growing prevalence and will become the leading cause of advanced liver disease and cirrhosis. Obesity has a negative impact on NAFLD at all aspects and stages of the disease. The growing epidemic will strain health care resources and demands new concepts for prevention, screening and therapeutic approaches. A better understanding of the interplay of liver, gut and hormonal system is necessary for new insights in the underlying mechanisms of NAFLD and the metabolic syndrome including obesity. Identification of patients at risk for progressive liver disease will allow a better adaption of treatment strategies.