Despite the physiological role of oxidant molecules, oxidative stress (OS) could underlie several human diseases. When the levels of antioxidants are too low or too high, OS occurs, leading to damage at the molecular, tissue and cellular levels. Therefore, antioxidant compounds could represent a way to modulate OS and/or to maintain proper redox balance. This review provides an overview of the methods available to assess total antioxidant capacity (TAC) in biological systems to elucidate the correct terminology and the pathophysiological roles. The clinical context is fundamental to obtain a correct interpretation of TAC. Hence, we discuss metabolic syndrome and infertility, two clinical conditions that involve OS, including the potential prognostic role of TAC evaluation in monitoring antioxidant supplementation. This approach would provide more personalised and precise therapy.