Insulin resistance (IR) and metabolic syndrome have recently been implicated in the pathogenesis and progression of chronic liver diseases, especially chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). In this review, we provide current information on their deleterious effect on the liver, with particular interest in those two entities. In NAFLD, IR causes both the accumulation of fat in hepatocytes and the progression to non-alcoholic steatohepatitis (NASH). Moreover, the presence of metabolic syndrome seems to be associated with severe fibrosis in NASH patients. In CHC, IR develops early in the course of the disease and precedes steatosis. It is also independently associated with histological severity and negatively affects treatment response, irrespective of genotype. Consequently, therapies targeting IR and metabolic syndrome could indirectly ameliorate the prognosis of both NAFLD and CHC. As specific therapies do not exist, patients with metabolic syndrome and CHC and NAFLD should be counseled to lose weight and ameliorate their glycemic control and lipid profile.