The first Cochrane systematic review examining the evidence on screening for prostate cancer was first published in 2006. The 2006 version of the Cochrane review identified two randomised controlled trials (RCTs), drawing the conclusion that there was insufficient evidence to either support, or refute, the use of screening versus no screening in reducing prostate cancer-specific morality. The most recent version of the review, published in 2013, assessed evidence from five RCTs. Based on the evidence from the five RCTs, the authors of the 2013 version concluded that screening did not significantly reduce prostate cancer-specific mortality. Of the five trials included in the 2013 Cochrane review, only two were assessed as being a low risk of bias - the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial. This chapter discusses the differences between the ERSPC and PLCO trials, and examines what issues may contribute to their conflicting results. It also aims to contextualise results from this most recent Cochrane systematic review and discuss the critique of the Cochrane systematic review raised by Schroder in the chapter entitled, "ERSPC, PLCO studies and critique of Cochrane review 2013".