One randomized, prospective clinical trial for chemoprevention of prostate cancer has been completed, and two additional trials are ongoing. The investment, time, and effort for these trials are substantial. We reviewed the outcomes of these trials to address the value of the investment. The outcomes of the Prostate Cancer Prevention Trial (testing finasteride) and the design of the Selenium and Vitamin E Cancer Prevention Trial (SELECT; testing vitamin E and selenium) trial as well as the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial (testing dutasteride) were reviewed. From a public health standpoint, there is tremendous potential for benefit from large-scale cancer prevention trials. Because of the volume of data that are collected, potential discoveries related to the biology of the disease are substantial. Translational scientific efforts are direct outgrowths of these studies. Prospective, randomized chemoprevention trials for prostate and other cancers are expensive and require long periods of time to conduct, yet the rewards are on a par with the investment.