The traditional Mediterranean diet is the heritage of millennia of exchanges of peoples and their cultures throughout the Mediterranean basin. Its origins sink into the past, in the eating habits of the Middle Ages, rooted in the ancient Roman and Greek traditions. The symbols of rural life, bread, wine, and oil are the staples of the diet, supplemented by sheep cheese, vegetables, very little fish and meat, with a strong preference for fish. The Arabs have been responsible for the introduction of new plants such as citrus, eggplant, spinach and spices. The Islamic culture therefore participates in the change and transformation of the cultural unity of the Mediterranean, and provides a decisive contribution to the new culinary model that is forming. Another event of great historical impact was the discovery of America by Europeans. This discovery is accompanied by the introduction of new components, such as potatoes, tomatoes, corn, peppers, as well as different varieties of beans. The tomato, in particular, became a symbol of the Mediterranean cuisine. The work of Ancel Keys in the 1950s established the Mediterranean diet as the original prototype for current dietary guidelines. Keys observed that the poor population of small towns in southern Italy was much healthier than the wealthy citizens of New York, and even of their own relatives who had emigrated in earlier decades in the United States. He suggested that this could depend on the diet, and set forth to validate his original insight, focusing his attention on the foods that made up the diet of these populations. This effort led to the famous “Seven Countries Study” (conducted in Finland, Netherlands, Italy, United States, Greece, Japan, and Yugoslavia), meant to document the relationship between life styles, nutrition, and cardiovascular disease in the different populations, and to prove scientifically, through cross-sectional studies, the nutritional value of the Mediterranean diet and its contribution to the health of the populations that adopted it. As a cultural model, the Mediterranean diet can be recommended for both its health benefits and its palatability. There are several variants of the diet, but some common components can be identified: high monounsaturated/saturated fat ratio; ethanol consumption at moderate levels mainly in the form of wine; high consumption of vegetables, fruit, legumes, and grains; moderate consumption of milk and dairy products, mostly in the form of cheese; low consumption of meat and fish with preference given to fish. Growing evidence demonstrates that the Mediterranean diet is beneficial to health; the evidence is stronger for coronary heart disease, but it also applies to cancer and, more recently, to cognitive decline. Results from recent interventional trials, provide a strong biomedical foundation for the beneficial effects of the Mediterranean diet.