When analysing the beneficial effects of phenolic compounds, several factors that exert a clear influence should be taken into account. The content of phenolic compounds in foods is highly variable, directly affecting individual dietary intake. Once ingested, these compounds have a greater or lesser bioaccessibility, defined as the amount available for absorption in the intestine after digestion, and a certain bioavailability, defined as the proportion of the molecule that is available after digestion, absorption and metabolism. Among the external factors that modify the content of phenolic compounds in food are the variety, the cultivation technique and the climate. Regarding functional foods, it is important to take into account the role of the selected food matrix, such as dairy matrices, liquid or solid matrices. It is also essential to consider the interactions between phenolic compounds as well as the interplay that occurs between these and several other components of the diet (macro- and micronutrients) at absorption, metabolism and mechanism of action levels. Furthermore, there is a great inter-individual variability in terms of phase II metabolism of these compounds, composition of the microbiota, and metabolic state or metabotype to which the subject belongs. All these factors introduce variability in the responses observed after ingestion of foods or nutraceuticals containing phenolic compounds.