Carotenoids are pigments found in plants and microorganisms, but not synthesized in animals. Fewer than 10% of the carotenoids can function as vitamin A precursors in mammals. Carotenoids and retinoids have chemical and metabolic similarities and differences, and some overlap in biological activities. Carotenoids in tissues reflect food choices. Carotenoids exhibit biological activities as antioxidants, affect cell growth regulation, and modulate gene expression and immune response. Epidemiologic evidence links higher carotenoid intakes and tissue concentrations with reduced cancer and cardiovascular disease risk, although results from clinical trials do not support beta-carotene supplementation as a strategy to reduce risk. Continued research in this area is likely to stimulate better intervention strategies with clinical and public health applications.