There are increasing number of evidences that regular exercise reduce risks of several morbidities like cancer, heart attack, type II diabetes, hypertension and slows down ageing process. The mechanism of pro-healthy effects of exercise is far from being completely understood. For example exercise increase insulin sensitivity in type II diabetics and this is related to activation of AMP kinase and increase biogenesis of mitochondria in skeletal muscle. Interestingly, increase in insulin sensitivity was also observed in patients, whose body iron stores has been reduced. The fact that exercise has been reported to influence body iron metabolism made us ponder the question whether many positive effects of exercise can be related to these changes. Iron is essential for most of cellular processes like energy metabolism, cell proliferation, synthesis of DNA and collagen, posttranslational modification of some proteins and many others. However, for our body iron like oxygen when in excess, is toxic. The elevated body iron reserves have been linked with an increased risk of health problems such as cancer, type 2 diabetes, and coronary artery disease. Total body iron accumulates when iron intake begins to exceed its loss. This data are confirmed by studies on animal models of iron-induced cancer, and diabetes. Life-style changes such as exercise, calorie restriction, a diet rich in iron chelators, and phlebotomy are all associated with the reduction of total body iron. These treatments lead to diminished risk of several morbidities. Nevertheless, studies on cell cultures demonstrated that the labile iron pool (LIP) mainly determines its toxicity rather than total amount of accumulated iron. The LIP level is regulated by several signaling pathways and gene expression. Thus, it is expected that even at a high concentration of intracellular iron, its toxicity is not obvious until a cell is able to maintain a low level of LIP. These data suggest that an effective control of body iron stores (diet, exercise, and possibly phlebotomy) would be a wise strategy for disease prevention.