This review summarises 25 years of investigations on antioxidants research in foods and biological fluids and critically analyses the merits and limitations of using the total antioxidant capacity (TAC) measurement in the metabolomic era. An enormous bulk of knowledge was produced regarding the antioxidant capacity of foods and large TAC databases were developed. A direct link between a food TAC value and any health benefit is erroneous and has led to several cases of consumer deception. However, the striking epidemiological evidence associating a high dietary TAC with some disease prevention and the availability of well‐constructed TAC databases deserve attention and must be taken into account to establish the usefulness of measuring TAC in both foods and biological samples. The in vivo TAC measurement, usually performed in plasma, is influenced by many external factors, such as dietary habits, as well as environmental and behavioural factors, which are integrated towards homeostatic control by fine physiological mechanisms with high inter‐individual variability. Therefore, plasma TAC cannot be considered as a unique biomarker of individual antioxidant status. However, the combined evaluation of plasma TAC with known markers of disease, individual metabolism, inflammation and genetics, as well as with markers of gut microbiota composition and activity, may lead to the identification of populations that are more responsive to food/diet TAC. In this framework, the appropriate use of TAC measurement both in food and in vivo can still provide support for the interpretation of complex phenomena and be a tool for sample screening when making a quick decision toward in‐depth research investigations. © 2018 Society of Chemical Industry