Substantial evidence supports the value of testosterone replacement therapy (TRT) in improving quality of life in men with proven aging male syndrome (AMS). Benefits of TRT include improved bone mineral density, reduced fracture risk, increased muscle mass, and improved mood, sense of well being, and libido, among others. There is currently a heated debate about the theoretical association between TRT and the initiation, progression, and aggressiveness of prostate cancer; however, this link has not been uniformly studied, and any results have been contradictory and nonconclusive. Although no clear evidence links TRT to prostate cancer, the possibility of increasing the risk of a clinical manifestation of a latent pre-existing malignancy can influence the decision about TRT use. Current recommendations are to exclude prostate cancer before initiating TRT in men over age 40 and to closely monitor men in the first year of testosterone replacement, followed by observation in subsequent years.