Prostate cancer is the most common cancer and the second leading cause of cancer-related deaths in American men. Although the use of the prostate-specific antigen (PSA) test for prostate cancer screening since the 1990s has led to increased early diagnoses, the most recent studies are in conflict about the risks and benefits of routine prostate cancer screening. Recently, evidence has emerged to support the use of the PSA test to lower mortality, but there is still concern that over-diagnosis may lead to over-treatment of cancers that would not significantly affect patients' health for several years. This article describes the results of important recent prostate cancer screening trials, the National Comprehensive Cancer Network and American Cancer Society screening guidelines, and discusses the implications for clinical practice.