The Mediterranean environment, and most of the Italian peninsula, presents some peculiarities in terms of crop response to O(3) since most physiological mechanisms activated upon O(3) exposure, such as stomatal closure, often overlap and interact with those that underlie plant adaptation to drought and hyperosmotic stress, which are typical of these environments. OTC and EDU experiments have demonstrated that O(3) causes strong yield losses when crops are grown without water limitations. However, exposure to water or saline stress significantly reduced O(3) effects on crop yield. In this review, we present the methodological approaches that have been used to study plant-ozone interactions in Italy as well as biochemical, physiological and agronomic responses for representative cropping systems of the Mediterranean climate.