Iron is an important metal in the complex biochemistry in human beings. However there are primary or secondary diseases that lead to an accumulation of iron in parenchymal organs and induce progressive and serious systemic harm. This review aims to define the fundamental steps of cell biology and physiology of iron and the pathophysiological mechanisms responsible for its accumulation in the parenchyma. In addition, we analyze the main primitive (hemochromatosis) and secondary (inflammation, liver diseases and hematological) diseases, responsible for the damage caused by iron, and we analyze the clinical consequences of iron overload. Furthermore, we pass under review a particular classification of general mechanisms and kinetics of iron overload responsible for its clinical phenotypes, dividing them into systemic, cellular and subcellular overload mechanisms. Finally we describe the main pathologic stages resulting from iron overload, with particular reference to liver damage and progression to hepatocellular carcinoma.