Beneficial health effects of olive oil and its phenolics are presented in light of the Mediterranean diet (MD), which is characterized by (1) a high intake of cereals, vegetables including leafy greens, legumes, nuts, and fruit; (2) a moderate intake of poultry, fish, eggs, milk and dairy products, as well as a regular but moderate ethanol consumption (generally in the form of wine during meals); and (3) a low intake of red and processed meat and industrial confectionary. Olive oil (OO) is the main fat used in all preparations of the MD. The health benefits of consuming OO have been known since antiquity and were traditionally attributed to its high MUFA content, mainly oleic acid. A large number of epidemiological and laboratory studies suggest beneficial and protective effects of OO in reduced risk of suffering cardiovascular disease (CVD) and cerebrovascular diseases, diabetes mellitus, metabolic syndrome, certain cancers, and neurodegenerative diseases. Potential effects of OO on various diseases-related parameters are discussed in relation to OO and its phenolics.