Analytical and immunological methodologies and occasionally both methodologies have been applied to detect and quantify 3-nitrotyrosine in almost every major organ system. In certain diseases increased levels of 3-nitrotyrosine have been correlated with elevated levels of other indices of oxidative stress. Numerous reports have established that nitration is a biological process derived from the biochemical interaction of nitric oxide or nitric oxide-derived secondary products with reactive oxygen species. This article addresses critical issues regarding this biological process, namely the biochemical pathways for nitration of tyrosine residuesin vivo,potential protein targets, and pathophysiological consequences of protein tyrosine nitration.