Natural antioxidant in vegetables, and in some animals have been studied by their action in the protection of a considerable number of diseases, such as, certain types of cancer, cardiovascular diseases, and age-related macular degeneration. Experimental evidences suggest that these compounds are important for protecting biological macro-molecules against oxidative damage. The search of new and more efficient antioxidants appears to be directed with carotenoids which have demonstrated that their consumption may reduce the incidence of certain diseases. In addition they represent a provitamin A source, and their actual antioxidant activity in the cell by participating in the neutralization of reactive oxygen species, and nitrogen produced, as a part of the cellular metabolism. This paper is focused to review basic and clinical aspects of investigations which have been associated with the intake of carotenoids with cancer, heart diseases, and age-related macular degeneration; the above all, we have tried to identify basic concepts of the role of the carotenoids and their metabolism; after that, we have reviewed clinical evidence that show how the intake of carotenoids reduces certain diseases. Finally, we discuss some of the results of investigation.