There is a fair amount of population-based evidence showing that soy isoflavones can protect against PCa. Unfortunately, the mechanisms supporting this association have not yet been resolved. Nonetheless, mechanistic explanations for how soy isoflavones can reduce cancer risk or disrupt the biology of transformed cells are increasing. Although the role of soy isoflavones in PCa has traditionally been linked with the suppression of proliferation and the induction of apoptosis, recently there is a compelling evidence that soy isoflavones regulate other cancer-related cellular processes. For example, a reasonable number of reports suggest that the antioxidant actions of soy isoflavones are worth exploring for cancer prevention. The breadth of these potential mechanisms by which soy isoflavones prevent or suppress cancer is given in Table 2. Still, many gaps remain beyond understanding of how soy isoflavones regulates cell biology relevant to PCa prevention and treatment. Most of the studies performed to assess the protective effects of soy isoflavones on PCa have used cells with mutant AR such as LNCaP, or cells that are devoid of AR such as PC-3 and DU-145. In addition, most of these studies used high pharmacological doses of genistein that do not reflect what can be achieved by people consuming soy rich diet. Similarly, there are few controlled animal studies that warrant the validity of proposed molecular mechanisms for soy isoflavone mediated cancer prevention using the ranges of soy isoflavones concentrations that are observed in human populations. Therefore, further studies must be conducted to determine if these mechanisms are different within the context of wild type AR and low physiological concentrations. Recent advances in global profiling of transcription factor-binding sites with techniques such as ChIP-seq should overcome this uncertainty, and help researchers to examine the differential effects of these isoflavones in the context of these pervasive AR mutations. Even with all of these gaps in our understanding, this is an unprecedented opportunity for research to explore mechanisms of action of soy isoflavones in preventing PCa.