Total Antioxidant Capacity (TAC) considers the cumulative action of all the antioxidants present in plasma and body fluids, thus providing an integrated parameter rather than the simple sum of measurable antioxidants. The capacity of known and unknown antioxidants and their synergistic interaction is, therefore, assessed, thus giving an insight into the delicate balance in vivo between oxidants and antioxidants. There is new evidence indicating the importance of understanding the mechanisms of the homeostatic control of TAC in plasma and tissues and its modification during oxidative stress development. Recently, the epidemiological application of TAC has been proposed as a new tool for investigating the relationship between dietary antioxidants and cancer risk in population studies. This review outlines the pros and cons of the more common assays for measuring plasma TAC and the latest findings on dietary modulation of plasma redox status. Finally, the feasibility of the 'TAC concept' as an innovative tool for investigating the association between diet and oxidative stress is discussed.