Nonalcoholic fatty liver disease (NAFLD) is generally considered as the hepatic manifestation of the metabolic syndrome (MS). Although there is no doubt that NAFLD is tightly linked to the MS, the diagnosis of NAFLD encompasses a broad range of histological entities and as a composite phenotype may be hindering attempts to understand the mechanistic basis of these variants. The awareness that NAFLD is not solely and invariably associated with the MS is a useful means to help direct future studies. We should be aware that mechanisms other than insulin resistance may contribute to the chronic inflammatory processes that underpin the development of liver fat accumulation and the subsequent architectural distortion of the liver. Further studies with special focus on hemoglobin as a risk factor for the development of NAFLD in the absence of MS should be performed.