Non-communicable diseases are currently the leading cause of mortality in the world. It is noteworthy that many cases of these complex diseases can be prevented through the consumption of a healthy diet. The Mediterranean diet (MD) is frequently considered as the dietary elixir that is effective in reducing the risk of non-communicable diseases and in improving longevity. In Chapter One, the authors review studies that have revealed interactions between MD and specific genetic variants that effectively reduce the risk of complex diseases. In Chapter Two, the Mediterranean diet in relation to its role in the prevention and management of cardiovascular disease is discussed. Chapter Three focuses on the nutrient and phytochemical profile of the Mediterranean diet and its effectiveness in the prevention and management cancer with details on mechanisms of actions. Chapter Four profiles the chemical characteristics and nutritive value of seafood caught in the Ionian Sea that is of high commercial interest in Mediterranean countries. To conclude, Chapter Five discusses the relationship of several different Mediterranean dietary patterns to the incidence of metabolic, cardio-vascular (including stroke), and the most frequent cancers. Beside the expected importance of plant foods and the necessary moderation of animal foods, this comparison unravels the peculiar effect of specific foods, either beneficial foods such as whole grains and olive oil, or detrimental foods such as energy-dense and nutrient-poor foods.