The Mediterranean lifestyle has traditionally been associated with a healthier life pattern, less prone to chronic illnesses, especially cardiovascular diseases. Among the different lifestyle variables, the concept of the Mediterranean diet (MedDiet) stands out as the healthiest aspect of the Mediterranean lifestyle. Moreover, although big differences in diet can be observed between the various countries on the Mediterranean coast, the Mediterranean lifestyle is also characterized by greater physical activity, mainly consisting of frequent walks encouraged by the warm and pleasant climate in comparison to central and northern Europe. So-called social support is also greater in the Mediterranean lifestyle with a closer and stronger family network and friends proving to be beneficial for health. However, there is great controversy about the Mediterranean siesta, mealtimes and sleep patterns. With regard to the MedDiet and despite the heterogeneity in the MedDiet definition, there is a commonly recognized pattern of consumption characterized by: a) high consumption of vegetables, fruits, cereals, legumes, nuts, and olive oil; b) moderate to high fish consumption; c) low consumption of red meats, and meat products; d) poultry and dairy products in moderate to small amounts and. There also seems to be a pattern of alcoholic and alcohol-free beverage consumption that varies depending on age. Environmental factors mainly contribute to this Mediterranean lifestyle, although genetic influences also interact. It is known that there are genetic variants that are associated with the intake of certain foodstuffs and among them the most relevant gene is the lactase gene (LCT) and its association with milk consumption. Thus, single nucleotide polymorphisms (SNPs) in the minichromosome maintenance complex component 6 (MCM6) gene are associated with differential transcriptional activation of the promoter of the neighboring lactase (LCT) gene and, thereby, influence lactase persistence (LP) in adulthood. The rs4988235 SNP, located at -13910 bp upstream from the LCT gene (-13910C>T) within intron 13 of the MCM6, has been the most studied SNP in relation to LP, milk intake and obesity-related diseases. Curiously, there is a north/south gradient in the prevalence of this gene variant, LP being less prevalent in the Mediterranean countries. Fruit, vegetable, sweets, sugared drinks, bitter drinks, etc. have been associated with variations in the different genes related to taste perception. There is increasingly detailed knowledge on the genes associated with the perception of sweet, bitter, sour, umami and salty tastes and their association with both food consumption, and the different health/disease phenotypes are being investigated. We have found associations between the perception of different tastes and the degree of adherence to the MedDiet. Moreover, diet itself may explain why certain gene variants are more prevalent in some countries than in others, as in the case of mutations in the MTHFR gene, which are more prevalent in Mediterranean countries than in northern Europe. In contrast, mutations in the APOE (E4 allele) are more frequent in northern Europe than in Mediterranean countries. To better understand these gene-diet interactions and their impact on the intermediate and final phenotypes of cardiovascular disease, we shall review several results from the PREDIMED (PREvencion con DIeta MEDiterranea) study. We have detected interesting gene-diet interactions in which greater adherence to the MedDiet, or to some of its typical foods, is able to reverse the adverse effects that the risk alleles have on the specific phenotypes.Although in nutrigenetics, the interactions of SNP candidates with total liquid intake in the diet are less well known and difficult to study, there are classic examples in monogenic diseases that point to their importance. Outstanding among these examples is that of cystinuria, an autosomic recessive genetic disorder characterized by an impairment in the transport of cystine, ornithine, lysine, and arginine. Of these, only cystine is insoluble enough to cause stone formation. It can lead to significant morbidity in affected patients due to the often large and recurrent resulting kidney stones. Incidence of cystinuria in the Spanish Mediterranean population is high and has a specific genetic pattern. Mutations in the amino acid exchanger System b(0,+), the two subunits of which are encoded by SLC3A1 and SLC7A9, predominantly underlie this disease. Our group showed a low prevalence of mutations in the SLC3A1 gene and a higher prevalence of mutations in the SLC7A9 gene, in contrast to that found in other countries. However, the wide variation of phenotypical traits suggests that further investigation into other genetic and/