Systemic and topical application of antioxidant substances for the medical treatment and prophylaxis of many diseases as well as additional protection of the skin against the destructive action of free radicals and other reactive species has become very popular during the past years. Stimulated by the positive results of a fruit and vegetable diet in supporting medical treatment and in cosmetics, artificial and extracted antioxidant substances have been broadly applied. Surprisingly, not only positive but also strong negative results have been obtained by different authors. According to study reports artificial and extracted antioxidant substances support different kinds of medical therapies, if they are applied in mixtures of different compounds at low concentration levels. In the case of the application of high concentration of some single compounds, side effects were often observed. Regarding skin treatment by systemically applied antioxidant substances for cosmetic purposes, positive cosmetic effects as well as no effects, but almost no side effects, apart from a number of allergic reactions, were reported. One reason for this seems to be the lower concentration of systemically applied antioxidant substances in comparison with a medical application. Topical application of antioxidant substances is closely related to cosmetic treatment for skin protection and anti-aging. Positive results were also obtained in this case. The present review is an attempt to classify and summarize the published literature concerning the efficiency of action of systemic and topical applications of antioxidant substances, such as carotenoids and vitamins, on human organism and especially on the skin. The available literature on this topic is very extensive and the results are often contradictory. Nevertheless, there are some clear tendencies concerning systemic and topical application of antioxidant substances in medicine and cosmetics, and we summarize them in the present paper.