The term antioxidant is one of the most confusing definitions in biological/medical sciences. In chemistry, antioxidant is simply conceived a compound that removes reactive species, mainly those oxygen-derived, while in a cell context, the conceptual definition of an antioxidant is poorly understood. Indeed, non-clinically recommended antioxidants are often consumed in large amounts by the global population, based on the belief that cancer, inflammation and degenerative diseases are triggered by high oxygen levels (or reactive oxygen species) and that through blocking reactive species production, organic unbalances/disorders can be prevented and/or even treated. The popularity of these chemicals arises in part from the widespread public mistrust of allopathic medicine. In fact, reactive oxygen species play a dual role in dealing with different disorders, since they may contribute to disease onset and/or progression but may also play a key role in disease prevention. Further, the ability of the most commonly used supplements, such as vitamins C, E, selenium, and herbal supplements to decrease pathologic reactive oxygen species is not clearly established. Hence, the present review aims to provide a nuanced understanding of where current knowledge is and where it should go.