The role of the transition metals such as iron and copper in oxidative modification of low-density lipoprotein (LDL), increasing its affinity for subendothelial macrophages and its atherogenicity, is well established experimentally. Whether increased iron stores are associated with a higher risk for coronary heart disease was tested in several cohort studies. Only those studies using proper indicators for body iron stores provided some evidence for the validity of this hypothesis [1]. There is no solid information on the chemical form, origin, and quantity of catalytically active iron able to promote oxygen-radical-mediated atherosclerosis. Because it is not justified to advocate iron chelation for therapy or prevention of atherosclerosis, we did not discuss this option in our review of iron-chelating agents in non-iron overload conditions [2]. Some practitioners justify their treatment of atherosclerosis by citing the iron-chelating property of EDTA. It is exactly this property that should preclude its use for any condition that may be associated with oxygen-radical-mediated tissue damage. Like deferoxamine, EDTA is a hexadentate ligand that offers six coordination sites to bind iron. Unlike deferoxamine, however, EDTA is too small to completely encompass the iron ion. A seventh coordination site is induced by distortion of the usual coordination symmetry [3], leaving iron in a catalytically active form. It is well known that iron-EDTA in a superoxide generating system catalyzes the formation of the hydroxyl radical [4]. We have recently shown the concentration-dependent hydroxyl-radical-generating properties of Fe(III)EDTA using electron paramagnetic resonance techniques [5]. The human body possesses many well-tuned scavenger mechanisms to prevent oxygen-radical-mediated damage. Many disease conditions can disturb this balance. Also, chelators that bind iron in a catalytically active form can have deleterious effects, especially at sites already in danger of oxygen-radical pathologic conditions. Drugs such as EDTA should therefore only be used in controlled studies with careful monitoring of calcium and iron metabolism and toxicity. No justification exists for the ongoing use of EDTA in patients with atherosclerotic vascular diseases.