Prostate cancer is the second leading cause of cancer deaths in men, therefore it is increasingly important to understand its biology and epidemiology. New approaches for the primary and secondary prevention of prostate cancer are needed, including innovative uses of chemoprevention. This review provides an overview of the epidemiological data suggesting that higher intakes of selenium may reduce the risk of prostate cancer. In addition, a discussion of preclinical data is presented. Special emphasis is placed on the following areas: (1) chemical forms of selenium and antitumorigenic activity, (2) in vitro effects of selenite versus monomethylated selenium, and (3) current clinical intervention trials with selenium in prostate cancer. Chemoprevention, especially with dietary forms of selenium, is a promising new approach that presently is undergoing intensive investigation.