The element selenium (Se) was recognized only 40 years ago as being essential in the nutrition of animals and humans. It is recognized as being an essential component of a number of enzymes, in which it is present as the amino acid selenocysteine. Se compounds have also been found to inhibit tumorigenesis in a variety of animal models, and recent studies indicate that supplemental Se in human diets may reduce cancer risk. The antitumorigenic activities have been associated with Se intakes that correct nutritionally deficient status in animals, as well as higher intakes that are substantially greater than those associated with maximal expression of the selenocysteine-containing enzymes. Therefore, it is proposed that while some cancer protection, particularly that involving antioxidant protection, involves selenoenzymes, specific Se metabolites, which are produced in significant amounts at relatively high Se intakes, also discharge antitumorigenic functions. According to this two-stage model of the roles of Se in cancer prevention, individuals with nutritionally adequate Se intakes may benefit from Se supplementation. Evidence for chemoprevention by Se and for the apparent mechanisms underlying these effects is reviewed to the end of facilitating the development of the potential of Se compounds as cancer chemopreventive agents.