Non-Alcoholic Fatty Liver Disease (NAFLD) is a common worldwide clinical and major public health problem affecting both adults and children in developed nations. Increased hepatic iron stores are observed in about one-third of adult NAFLD patients. Iron deposition may occur in parenchymal and/or non-parenchymal cells of the reticuloendothelial system (RES). Similar patterns of iron deposition have been associated with increased severity of other chronic liver diseases including HCV infection and dysmetabolic iron overload, suggesting there may be a common mechanism for hepatic iron deposition in these diseases. In NAFLD, iron may potentiate the onset and progression of disease by increasing oxidative stress and altering insulin signaling and lipid metabolism. The impact of iron in these processes may depend upon the sub-cellular location of iron deposition in hepatocytes or RES cells. Iron depletion therapy has shown efficacy at reducing serum aminotransferase levels and improving insulin sensitivity in subjects with NAFLD.