Iron is an essential element for normal cellular function and general health. However, iron may play a pathologic role in certain cardiac conditions including reperfusion injury, hemochromatosis, beta-thalassemia and coronary atherosclerosis. It also may play a role in injury due to anthracycline cardiotoxicity. Removal of iron via phlebotomy for hemochromatosis and chelation therapy for beta-thalassemia are proven treatments. Cell culture, and isolated organ and animal studies suggest that depleting iron stores may prevent reperfusion injury, restenosis and even atherogenesis. This article will review mechanisms by which iron overload states and normal iron stores contribute to cardiovascular pathophysiology and the accumulating evidence that iron chelation may prevent restenosis and atherogenesis.