Advanced imaging technologies play a central role in screening asymptomatic patients. However, the balance between imaging-based screening's potential benefits versus risks is sometimes unclear. Radiologists will have to address ongoing concerns, including high false-positive rates, incidental findings outside the organ of interest, overdiagnosis, and potential risks from radiation exposure. In this article, we provide a brief overview of these recurring controversies and suggest the following as areas that radiologists should focus on in order to tip the balance toward more benefits and less harms for patients undergoing imaging-based screening: interpretive variability, abnormal finding thresholds, and personalized, risk-based screening.