Technical Abstract: The complete, 13 year, results of the Nutritional Prevention of Cancer Trail have been analyzed, causing some speculation over the robustness of the previously reported findings of reduction of cancer risks by supplements of 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 the 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 PSA level. Recent sub-group analyses showed Se-supplementation to reduce risk to that cancer mostly among subjects who entered the trail 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 anti-angiogenic effects. Thus, a body of basic understanding is developing by which to understand and evaluate the results of the NPC and future clinical trials. That understanding will also need to include the mechanisms of Se transport and cellular uptake so that appropriate inferences can be made from findings from cell culture systems which have 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 also safe, accessible and sustainable.