The anti-androgenic activity of the ethanol extract of the fruiting body of Ganoderma lucidum has been previously reported. Ganoderol B with 5alpha-reductase inhibitory activity and the ability to bind to androgen receptor (AR) can inhibit androgen-induced LNCaP cell growth and suppress regrowth of the ventral prostate induced by testosterone in rats. The down-regulation of AR signaling by ganoderol B provides an important mechanism for its anti-androgenic activity. In view of the fact that PSA (prostatic specific antigen, a well-accepted prognostic indicator of prostate cancer) is down-regulated, an important implication of this study is that ganoderol B intervention strategy aimed at toning down the amplitude of androgen signaling could be helpful in controlling morbidity of prostate cancer. In conclusion, our result suggests that ganoderol B might be useful in prostate cancer and benign prostatic hyperplasia (BPH) therapy through suppressing the function of androgen and its receptor.