Hemoglobin has functions besides carrying oxygen to the tissues, and regulates vascular tone and inflammation via a redox couple with methemoglobin. Hemoglobin has iron in the reduced valance Fe(II) and methemoglobin has iron in the oxidized valance Fe (III), with a free energy capable of producing water from oxygen. In generating methemoglobin the couple functions as a nitrite reductase. The degree of oxidation of hemoglobin senses the oxygen level in the blood and uses its ability to produce nitric oxide from nitrite to control vascular tone, increasing blood flood when the proportion of oxygenated hemoglobin falls. Additional cardiovascular damage is produced by methemoglobin mediated oxidation of light density lipoproteins, accelerating arteriosclerosis. In addition, the release of heme from methemoglobin is an important factor in inflammation. These physiologic functions are paralleled by thewell‐described role in the oxidation of various drugs resulting in methemoglobinemia. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.