Although essential for cell physiology, an increase or depletion of body iron has harmful effects on health. Apart from iron deficiency anemia and iron overload-related organ tissue damage, there are increasing evidences that body iron status is implicated in atherosclerotic cardiovascular diseases. The hypothesis formulated in 1981 that iron depletion may protect against cardiovascular events is intriguing and has generated a significant debate in the last two decades. Indeed, to study this phenomenon, several investigators have tried to design appropriate experimental and clinical studies and to identify useful biochemical and genetic markers of iron status. The results of the literature on the effect of iron deficiency and overload on vascular health are critically reviewed in this study from a pathogenic and clinical point of view.