The aim of this chapter is to provide a brief overview of the recent results of studies on extra virgin olive oil (EVOO) and its interactions with other food ingredients during cooking, to highlight basic molecular aspects of the ‘magic’ of EVOO and its role in Mediterranean gastronomy. The use of raw EVOO added to foods after cooking (or as a salad oil) is the best way to express the original flavour and to maximize the intake of natural antioxidants and compounds related to positive effects on human health (hypotensive, antiinflammatory, and anti-cancerogenic, among others). EVOO, however, also exhibits its protective properties during/after cooking. Different chemical interactions between biophenolic compounds and other food ingredients (water, milk proteins, carotenoids of tomato, omega-3 polyunsaturated fatty acids in canned-in-oil fish and meat or fish proteins) occur. Even during cooking, EVOO exhibits strong antioxidant properties and influences the overall flavour of cooked foods. The physical (partitioning, emulsion) and chemical (hydrolysis, covalent binding, antioxidant properties) phenomena occurring during cooking of EVOO are discussed with emphasis on the changes in the sensory (bitterness and fruity flavour) and nutritional qualities of some traditional Mediterranean foods. In particular, tomato–oil interactions during cooking, fish canning in EVOO, meat marinated in EVOO before cooking and roasting and frying in EVOO are examined. The interactions between EVOO antioxidants and flavours with milk proteins are also briefly discussed.