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Screening has long been portrayed as an inherently beneficial activity that saves lives, rather than as a complex mixture of potential benefits and harms that must be carefully weighed for each modality. The early success of the Pap smear in reducing deaths from cervical cancer may have inadvertently fostered simplistic messaging about unqualified benefits of screening. Over time, large-scale randomized controlled trials (RCTs) of prostate and other cancers have highlighted the potential harms caused by mass screening programs (especially those related to overdiagnosis and unnecessary treatment) and have revealed the counterintuitive elements involved in evaluating such programs. The criteria for evaluation now extend beyond the performance criteria of the test itself to include the net balance of benefits, risks, and costs. PSA screening, widely used in the United States since the late 1980s, has now been removed from the list of routinely recommended procedures, based on evidence from RCTs.