Accumulated epidemiological evidence indicates that prostate cancer mortality should be preventable. As androgenic hormones have long been recognised to be required for normal prostatic development, and because androgen deprivation is an established treatment for advanced prostate cancer, androgen signalling has been an attractive target for prostate cancer prevention. Inhibitors of 5alpha-reductase, an enzyme necessary for the conversion of testosterone to the more potent androgen dihydrotestosterone, have reached pivotal clinical trials for prostate cancer prevention. In addition, new insights into the molecular pathogenesis of prostate cancer hint that chronic or recurrent prostate inflammation may contribute to the development of the disease. A variety of antioxidants and anti-inflammatory drugs, which are likely to be capable of attenuating pro-carcinogenic genome damage from reactive oxygen and nitrogen species, are also under current development for prostate cancer prevention. This review will consider the rational development of these and other new agents and approaches for prostate cancer prevention in the context of recent research progress in ascertaining the aetiology of prostate cancer.