There is growing evidence that cardiovascular disease is associated with progressive changes in the production of free radicals and radical-derived reactive species. These intermediates react with all major cellular constituents and may serve several physiological and pathophysiological functions. The nitration of protein tyrosine residues has been used as a footprint for in vivo production of radical and nonradical reactive species. Tyrosine nitration may alter protein function and metabolism and therefore, provides for further dysfunctional changes. This review focuses on an appearance of tyrosine nitrated proteins in cardiovascular tissues under different settings of cardiovascular disease. Sources of reactive species, putative mechanisms of protein nitration in vivo, as well as protein nitration under normal physiological conditions, are also described. The goal of this review is to attract more attention to identification of specific proteins, which undergo tyrosine nitration and to study a correlation between their altered function and pathology. Understanding how protein nitration affects disease progression may offer a unique option for design of antioxidant therapy for the treatment of cardiovascular complications. At the same time, protein nitration can be a biological marker of efficiency of antioxidant therapy.