Over the recent years, researches have focused their attention on the pathologic role of free radicals in a variety of diseases, among which the most important are atherosclerosis, cancer, and diabetes. The set of intracellular and extracellular conditions that leads to chemical or metabolic generation of reactive species is termed "oxidative stress." The susceptibility to oxidative stress is a function of the overall balance between the factors that exert oxidative stress and those that exhibit antioxidant capability. There is currently great interest in the potential contribution of increased oxidative stress to the development of complications in diabetes mellitus. Direct measurement of oxidative stress in vivo is a very complex question, because free radicals are highly reactive, have a very short life, and are present in very low concentrations. Thus, indirect methods, used for measuring secondary products of oxidative stress, are rather unspecific and may give conflicting data. Nitrotyrosine detection in plasma and tissues may be a useful method to demonstrate peroxynitrite-mediated damage. The total radical-trapping potential (TRAP) in plasma represents a more reliable estimation of serum antioxidant capability than the measurement of each known antioxidant. The detection of increased levels of oxidation products in tissue and biological fluids is important to investigate the relation between free radical production and the development of pathology. This hypothesis suggests the possibility of a therapeutic intervention with antioxidant agents. The identification of a useful marker to assess the effect of antioxidants on oxidative stress seems to be mandatory.