The complete, 13 years, results of the Nutritional Prevention of Cancer Trial have been analysed, causing some speculation over the robustness of the previously reported findings of reduction of cancer risks by supplements of selenium (Se) to a cohort of older Americans. These analyses confirmed that Se supplementation was associated with marked reductions in risks to total (all-site except skin) carcinomas and to cancers of the prostate and colon-rectum. Of those deep-site treatment effects, the most robust was for prostate cancer, which was more frequent, and was confirmed by serum prostate-specific antigen level. Recent subgroup analyses showed Se supplementation reduced risk of cancer mostly among subjects who entered the trial with plasma Se levels in the bottom tertile of the cohort. Other recent findings have demonstrated that Se treatment can promote apoptosis in prostate cancer cells and, possibly, impair their proliferation through antiangiogenic effects. Thus, a body of basic understanding is developing by which one can understand and evaluate the results of the Nutritional Prevention of Cancer and future clinical trials. This understanding also requires inclusion of the mechanisms of Se transport and cellular uptake, so that appropriate inferences can be made from findings from cell culture systems, which tended to use effective Se doses much larger than relevant to cells in vivo. Also needed is information on the chemical speciation of Se in foods, so that Se delivery can be achieved in ways that are effective in reducing cancer risk and is also safe, accessible and sustainable.