Nitrotyrosine has been identified as an indicator of cell damage and inflammation, as well as the production of NO. Nitrotyrosine is a relatively stable product formed from various reaction pathways. One of them is the reaction of peroxynitrite with tyrosine. Peroxynitrite formed from superoxide and nitric oxide radicals mediates tyrosine nitration reactions on proteins resulting in inactivation of certain house-keeping enzymes as well as endogenous antioxidant enzymes such as catalase and superoxide dismutase. Nitrotyrosine has been implicated in the pathogenesis of many inflammatory, infectious and degenerative human diseases such as Alzheimer’s disease, atherosclerosis, asthma and a variety of conditions mediated by endothelial injury. Oxidative stress has been indicated as a mechanism of secondary neuronal injury in traumatic brain injury. Nitrotyrosine in the cerebrospinal fluid may be an in vivo marker of oxidative nitric oxide damage. Several pathologies of the cardiovascular system are also associated with an augmented production of nitric oxide and/or superoxide-derived oxidants that lead to nitroxidative stress. The high contents of iron (heme) in certain tissues such as heart and vascular smooth muscle cells could serve as a biological base for iron toxicity on free radical-mediated tissue damage, including formation of nitrotyrosine.