The long-standing concern that testosterone replacement therapy (TRT) may increase the risk of prostate cancer (PCa) has come under new scrutiny. Arguments used to support this concern lack a scientific basis. The original assertion by Huggins that administration of testosterone (T) caused “enhanced growth” of PCa was based on only a single patient. New evidence suggests that TRT has little, if any, negative impact on the prostate, even in men with a history of PCa. A saturation model is proposed that is consistent with regression of cancer when T is reduced to castrate levels and with lack of observed growth when serum T is increased.