Predicting antioxidant activity in a given system is undoubtedly the "holy grail" of the academic and industrial research, especially for phenolics which are the most abundant and widespread antioxidants on earth. However, this tour de force necessitates knowing the physicochemical traits that govern the antioxidant activity, which is still out of reach. From a chemical standpoint, phenolic antioxidants are able to give electrons to reactive species such as free radicals (among others). This is the basis of their antioxidant properties that make the hype on polyphenols in the scientific literature. However, do we know exactly what make them poor or excellent antioxidants? This mini-review will discuss the complexity of factors determining the antioxidant activity of phenolics. Above all, we will ask some crucial questions nobody usually asks. Are reducers necessarily antioxidants? When studying the quantitative structure-activity relationship, do we take into account the antioxidant activity of the oxidation product(s) of phenolics? How can we predict antioxidant activity in natural multiphasic systems if most of the studies come from artificial homogenous solutions? Finally, we think that scientists are too focused on reactivity, whereas the physico-chemistry behind phenolic antioxidants may be rather the key to understand the hitherto unknown antioxidant activity determinants.