The colorful group of compounds known as carotenoids are present in many plants, where they provide photoprotection and act as accessory pigments in photosynthesis. Many epidemiologic studies have shown strong associations between diets rich in carotenoids and a reduced incidence of many forms of cancer, and that finding led to the suggestion that the antioxidant properties of those compounds might help protect immune cells from oxidative damage, thus enhancing their ability to detect and eliminate tumor cells. Since the early 1980s, there have been reports supporting that hypothesis. However, more recently, after large prospective studies did not show protective effects of beta-carotene supplementation, more attention has been given to studies defining optimal levels of intake that can be achieved within a well-balanced diet. The latest intervention studies have suggested that, in well-nourished, healthy individuals, a moderate level of carotenoid supplementation is neither beneficial nor harmful. However, supplementation might be appropriate in undernourished or less healthy individuals, particularly if they are elderly. Future studies comparing supplements with real foodstuffs, combined with postgenomic technologies, will help define optimal intakes for different sectors of the population.