In the United States, prostate cancer will affect 1 man in 6 during his lifetime. Since the mid-1980s, screening with the prostate–specific antigen (PSA) blood test has more than doubled the risk of a prostate cancer diagnosis. A decrease in prostate cancer death rates has been observed since that time, but the relative contribution of PSA testing as opposed to other factors, such as improved treatment, has been uncertain. The recent release of 2 large randomized trials suggests that if there is a benefit of screening, it is, at best, small. Methods to assess a man's risk of prostate cancer, including those tools that integrate multiple risk factors, are now available and should be used in risk assessment. Men undergoing screening for prostate cancer may reduce their risk of prostate cancer with finasteride. CA Cancer J Clin 2009;59:264-273. © 2009 American Cancer Society, Inc.