The Mediterranean diet, one of the best-studied dietary patterns, was developed as a result of sociocultural, political, religious, agricultural, and economic influences overtime in a geographical region. The Seven Countries Study established the association between the eating patterns of Mediterranean countries with longevity and reduced risk of cardiovascular disease (CVD) compared to northern European countries and the USA over follow-up for 25 years. Since that study, numerous epidemiological studies have supported the health benefits and disease prevention effects of adherence to the Mediterranean diet. The dietary pattern associated with the Mediterranean diet is based on olive oil (mainly extra-virgin or virgin olive oil) as the main source of fat, whole grains, legumes, fruits, vegetables, nuts, and fish, wine in moderation, and a moderate intake of lean fresh meat, and dairy products, which provide an important source of minerals, vitamins, antioxidants, mono and polyunsaturated fatty acids (MUFAs and PUFAs), and fiber. This chapter reviews the available evidence of the benefits of the Mediterranean diet and the Mediterranean lifestyle in health through its impact on different chronic diseases, including cardiovascular diseases, metabolic syndrome, type-2 diabetes, chronic kidney disease, and neurodegenerative diseases.