Several lines of evidence point to olive oil and the olive oil-centered Mediterranean diet as conducive to longevity. The evidence stems from ecological, as well as analytic epidemiological studies assessing olive oil, monounsaturated lipids or the Mediterranean dietary pattern in relation to the incidence of, or mortality from, major common diseases, or overall mortality. Mechanistic considerations are addressed by biochemical studies, whereas randomized clinical trials provide further support to the evidence generated from observational investigations. The content of olive oil in several microcomponents with antioxidant potential, as well as its high content in monounsaturated lipids appear to be essential for the beneficial effect of this food.