In recent years, there has been a tremendous expansion in medical and dental research concerned with free radicals, reactive oxygen species, and anti-oxidant defense mechanisms. This review is intended to provide a critical, up-to-date summary of the field, with particular emphasis on its implications for the application of "anti-oxidant therapy" in periodontal disease. We have reviewed the nomenclature, mechanisms of actions, features, and sources of most common free radicals and reactive oxygen species, as well as analyzed the typical biological targets for oxidative damage. Based on a review of direct and indirect anti-oxidant host defenses, particularly in relation to the key role of polymorphonuclear neutrophils in periodontitis, we review current evidence for oxidative damage in chronic inflammatory periodontal disease, and the possible therapeutic effects of anti-oxidants in treating and/or preventing such pathology, with special attention to vitamin E and Co-enzyme Q.