Epidemiological evidence supports a health‐promoting effect of the Mediterranean Diet (MedDiet), especially in the prevention of cardiovascular diseases. These cardiovascular benefits have been attributed to a number of components of the MedDiet such as monounsaturated fatty acids, antioxidant vitamins and phytochemicals. However, the underlying mechanisms remain unknown. Likewise, little is known about the genes that define inter‐individual variation in response to the MedDiet, although the TCF7L2 gene is emerging as an illustrative candidate for determining relative risk of cardiovascular events in (...) response to the MedDiet. Moreover, omics technologies are providing evidence supporting potential mechanisms, some of them implicating epigenetics (i.e. microRNAs, methylation), and certain data suggest that some traditional foods could contribute via microRNAs possibly acting as exogenous regulators of gene expression. Future research should aim at increasing and consolidating the nutrigenetic and nutrigenomic knowledge of the MedDiet in order to provide sound, personalized and optimized nutritional recommendations. (shrink)