Numerous experiments have demonstrated that selenium supplementation to the diet at modest and nontoxic levels is an effective inhibitor of mammary tumorigenesis in mice and rats. In mice, selenium is most effective during the early stages of tumorigenesis, in particular the events surrounding the induction and expression of the preneoplastic transformation. Whereas selenium is an effective chemopreventive agent, there is little data to support its role as an effective therapeutic agent. The mechanisms of selenium-mediated inhibition of tumorigenesis have not been established. However, the available data suggest that selenium does not act by way of the principal selenoprotein in the cell, glutathione peroxidase, nor does selenium inhibit lipid peroxidation. A number of different mechanisms to explain the inhibitory effects of selenium are discussed; however, definitive answers await further experiments.