Over the last decades, a considerable body of evidence supported the hypothesis that diet and dietary factors play a relevant role in the occurrence of diseases. To date, all the major scientific associations as well as the World Health Organization and the nonscientific organizations place an ever‐increasing emphasis on the role of diet in preventing noncommunicable diseases. Many studies have evaluated the associations between food groups, foods, or nutrients and chronic diseases, and a consensus about the role of nutritional factors in the etiology of common diseases, such as cardiovascular and neoplastic diseases, has gradually emerged. Indeed, data from analytical and experimental studies indicated a relation between increased consumption of some food categories such as fruits and vegetables, fiber and whole grains, fish, and moderate consumption of alcohol and reduced risk of major chronic degenerative diseases, whereas increased total caloric intake, body weight, meat, and fats are associated with greater risk. However, the appropriate dietary strategy to prevent chronic degenerative diseases remains a challenging and a highly relevant issue. Recently, Mediterranean diet has been extensively reported to be associated with a favorable health outcome and a better quality of life. In the present review, we encompass the updated evidence of the beneficial effects of Mediterranean diet in the occurrence of major chronic degenerative diseases. © 2013 BioFactors, 39(4):335–342, 2013