Vitamin A deficiency significantly contributes to morbidity and mortality from infections among children and pregnant women, thus representing a crucial factor in the development of preventable childhood blindness, mostly affecting the poorest populations of low and middle income countries. In particular, a high prevalence of vitamin A deficiency is observed in developmental countries of tropical and subtropical regions. In such countries, the enhanced consumption of local fruits rich in provitamin A carotenoids was proposed by the World Health Organization of the United Nations for diminishing vitamin A deficiency, since such carotenoids like ?-carotene are efficiently metabolized to vitamin A by humans. In developed countries where vitamin A deficiencies are rare, dietary intake of carotenoids was also recommended due to numerous potential health benefits beyond vitamin A supply. For instance, frequent consumption of lycopene-rich foods like tomato products was associated with a lower incidence of cardiovascular disease and cancer.The presented work revealed the outstandingly high potential of red- and yellow-fleshed fruits from diverse papaya genotypes for providing highly bioavailable provitamin A carotenoids (?carotene, ?cryptoxanthin) and lycopene. An approach "from the farm to the fork" has been applied, investigating the natural diversity of available papaya fruits, horticultural aspects regarding carotenoid accumulation in papayas, carotenoid biosynthesis in papaya, in vitro digestion simulations of fresh and processed fruits, and a human clinical trial for the comparative assessment of carotenoid bioavailability from papaya, carrot, and tomato. Post-prandial carotenoid bioavailability was significantly higher from red-fleshed papaya as compared to carrot and tomato. The deduced hypothesis for explaining the high bioavailability from papaya may be transferred to other fruits and vegetables. Representing a robust pioneer species, Carica papaya L. can be easily cultivated in tropical and subtropical regions, where large parts of the poorer population often suffer from vitamin A deficiency. In the affected countries, an enhanced utilization and consumption of papaya fruits may help diminishing this most prevalent but avoidable deficiency together with its severe implications for human health.