The “free radical” theory of ageing is based on the fact that the deleterious effects of an excessive production of free radicals produced during aerobic metabolism cause oxidative stress, damaging biomolecules, cell structure, and function. It is widely believed that the release of free radicals, either as a by-product of normal metabolism or associated with inflammatory reactions, can contribute to a number of age-related diseases such as cardiovascular disease and cancer. Several ecological, case-control, and cohort studies indicate that diets rich in plant foods might reduce age-related disease development. Among a number of mechanistic hypotheses, diet-derived antioxidants have been proposed to contribute to explain these findings. However, contrasting results from intervention trials have raised strong concerns about the influence of antioxidants on human health. A vulnerable point of the research on antioxidants is the lack of information on the effect of the whole array of dietary antioxidants in disease prevention, because so far mainly single molecules have been investigated. Epidemiological and experimental evidence is mounting on the potential importance of the so called total antioxidant capacity (TAC). TAC represent a direct measurement of the nonenzymatic antioxidant network considering single antioxidant activity and the synergistic interactions of the redox molecules present in the tested matrix. This chapter describes the results of the main clinical trial involving galenic antioxidants, discussing the importance of properly assessing endogenous and dietary TAC to obtain an integrated and realistic portrait of the complex interactions at the basis of the postulated antiageing effect of antioxidants molecules.