Insulin resistance is the basis of both non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), the two conditions are often found in the same individual. The mortality of patients with NAFLD is significantly higher than that among the general population and cardiovascular risk may compete with liver-related risk in dictating the final outcome. Recent prospective studies have reported that NAFLD is associated with an increased incidence of MetS and type 2 diabetes mellitus, independent of obesity and other components of MetS. Thus, NAFLD may not only be a liver disease but also an early mediator of type 2 diabetes mellitus and MetS. The biological mechanisms by which NAFLD contributes to a higher risk of developing metabolic disorders are not fully understood. However, the fatty liver could contribute in the same way as visceral adipose tissue to insulin resistance, systemic inflammation and oxidative stress, while the decreased serum adiponectin concentrations might also be part of the mechanism. In contemporary clinical practice, it has become mandatory to evaluate the metabolic risk factors in NAFLD patients and to consider careful surveillance and aggressive treatment, not only of the resultant liver disease, but also of the possible underlying metabolic and vascular complications. Future studies might address the question whether earlier adjustment to a more efficient lifestyle or a pharmacological treatment that mobilizes fat out of the liver could reduce these risks.