There is growing evidence that normal or only mildly increased amounts of iron in the liver can be damaging, particularly when they are combined with other hepatotoxic factors such as alcohol, porphyrogenic drugs, or chronic viral hepatitis. Iron enhances the pathogenicity of microorganisms, adversely affects the function of macrophages and lymphocytes, and enhances fibrogenic pathways, all of which may increase hepatic injury due to iron itself or to iron and other factors. Iron may also be a co-carcinogen or promoter of hepatocellular carcinoma, even in patients without HC or cirrhosis. Based on this and other evidence, we hope that the era of indiscriminate iron supplementation will come to an end. Bloodletting, a therapy much in vogue 2 centuries ago, is deservedly enjoying a renaissance, based on our current understanding of the toxic effects of iron and the benefits of its depletion.