The beneficial effects of a high intake of tomatoes and tomato products on the risk of certain chronic diseases have been presented in many epidemiologic studies, with the suggestion that lycopene (a major carotenoid in tomatoes) is a micronutrient with important health benefits. Within the past few years, we have gained greater knowledge of the metabolism of lycopene and the biological effects of lycopene derivatives. In particular, the characterization and study of β-carotene 9',10'-oxygenase has shown that this enzyme can catalyze the excentric cleavage of both provitamin and non-provitamin A carotenoids to form apo-10'-carotenoids, including apo-10'-lycopenoids from lycopene. This raised an important question of whether the effect of lycopene on various cellular functions and signaling pathways is a result of the direct actions of intact lycopene or its derivatives. Several reports, including our own, support the notion that the biological activities of lycopene can be mediated by apo-10'-lycopenoids. More research is clearly needed to identify and characterize additional lycopene metabolites and their biological activities, which will potentially provide invaluable insights into the mechanisms underlying the effects of lycopene in humans.