Consumption of dietary carotenoids, plant pigments found in green, yellow, and orange fruits and vegetables, has been linked to decreased risk of cancer. Several intervention trials with beta-carotene, however, have failed to confirm this association. Indeed, in current smokers, beta-carotene appeared to increase risk. These disturbing results have not been explained. Laboratory studies with experimental animals and cells in culture have shown cancer preventive activity for a diverse range of carotenoids. Studies using human and animal cells have identified a gene, connexin 43, whose expression is upregulated by chemopreventive carotenoids and which allows direct intercellular gap junctional communication (GJC). GJC is deficient in many human tumors and its restoration or upregulation is associated with decreased proliferation. This review will focus on the growing body of evidence that carotenoids have unexpected biologic effects in experimental systems, some of which may contribute to their observed cancer preventive properties in models of carcinogenesis.