Oxidative stress results from an imbalance, an excess of oxidants, depletion of antioxidants or failure to repair oxidative damage induced by reactive oxygen species. A vast amount of evidence implicates oxygen-derived free radicals and high-energy oxidants as mediators in many pathological conditions of inflammation, shock, and organ responses to ischemia/reperfusion, which arise during a number of clinical surgical interventions, including transplant graft rejection and coronary bypass surgery, and in such diseases as, diabetes, atherosclerosis, hypertension, organ ischemia/reperfusion, cardiovascular inflammation, cardiac/brain infarction, cancer, pulmonary emphysema and autoimmune diseases. To eliminate or attenuate oxidative stress, antioxidant therapies have been developed and may be of great help to these patients. This review describes recent developments in the field of oxidative stress research and antioxidant function, summarizes new pharmacological strategies that are ongoing in antioxidant therapy with small molecules, free radical-scavenging enzymes, superoxide dismutases, catalase mimetics, flavonoids, vitamins and poly polymerase inhibitors, and presents experimental and clinical evidence of the role of antioxidants in diseases.