Nitrite is an intrinsic signaling molecule. Its ability to form nitric oxide (NO) under hypoxic conditions as well as its ability to form S-nitrosothiols under normoxic conditions has transformed this once inert anion into a critical molecule in maintaining NO and nitroso homeostasis throughout the entire physiological oxygen gradient in vivo in addition to serving as the endocrine mediator of NO. Steady state plasma nitrite has historically been used as a biomarker of NO availability. However, tissue specific metabolism of nitrite along with differences in nitrite and nitrate intake from diet warrant a careful assessment of plasma nitrite as an index of NO biochemistry. Metabolism and regulation of NO and nitrite are at the local cellular and tissue level dependent upon cellular redox status, redox active metal and thiol availability. Understanding nitrite metabolism and mechanisms of cytoprotection may offer novel means to prevent cardiovascular disease or limit injury from a cardiovascular event. Here the state of the art of nitrite in cytoprotection as well as maintenance of steady state blood and tissue nitrite is reviewed.