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Objective: The purpose of this review is to discuss some critical issues of isoflavones protective against the development of prostate cancer (PCa).Data Sources: Data cited in this review were obtained primarily from PubMed and Embase from 1975 to 2015.Study Selection: Articles were selected with the search terms isoflavone, Phytoestrogen, soy, genistin, and PCa.Results: Isoflavones do not play an important role on prostate-specific antigen levels reduction in PCa patients or healthy men.The effect ofisoflavones on sex hormone levels and PCa risk may be determined by equol converting bacteria in the intestine, specific polymorphic variation and concentrations of isoflavones.The intake of various types of phytoestrogens with lower concentrations in the daily diet may produce synergistic effects against PCa.Moreover, prostate tissue may concentrate isoflavones to potentially anti-carcinogenic levels.In addition, it is noteworthy that isoflavones may act as an agonist in PCa.Conclusions: Isoflavones play a protective role against the development of PCa.However, careful consideration should be given when isoflavones are used in the prevention and treatment of PCa.