Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disease ranging from simple steatosis to non-alcoholic steatohepatitis, is increasingly recognized as the hepatic manifestation of metabolic syndrome and is an important cause of liver-related morbidity and mortality. It is among the most common forms of liver disease. NAFLD reflects abnormal partitioning of fat, such that fat deposition is increased in the liver, and provides a link between NAFLD and the metabolic syndrome, a constellation of metabolic disorders that can also be associated with visceral fat or central adiposity. Together, the features of the metabolic syndrome presage overt diabetes and increase cardiovascular risk. Hepatitis C virus (HCV) appears to exacerbate the metabolic syndrome by eliciting increased insulin resistance (IR) and promoting truncal obesity. Moreover, the concomitant presence of HCV and NAFLD is associated with an increased likelihood of diabetes, hypertension and/or hypertriglyceridaemia. Metabolic abnormalities have been shown to influence response to treatment such that the presence of IR or obesity reduces the likelihood of a sustained virological response (SVR); conversely, SVR has been demonstrated to ameliorate IR and improve β-cell function. Clinically, these data suggest that attention must be paid not only to optimizing antiviral response but also to screening for and treatment of the various components of the metabolic syndrome.