This volume of Epidemiologic Reviews continues a discussion about screening within the evidence community that has been going on for many years. From various perspectives, the authors of these reviews consider the benefits and harms of screening for multiple conditions; the balance between benefits and harms (and costs) is often not clear. With few exceptions, the contribution of screening to improving the health of the public is small, yet it has become a popular and growing form of prevention. It may be that we are learning that the magnitude of benefit from screening is less than we hoped, and the harms may be greater than we thought. Perhaps we should not think of screening as our primary prevention strategy but rather use screening to make a real, but limited contribution to population health for a few conditions. We might target screening to smaller subpopulations with the highest potential benefit and the lowest potential harm. The payoff for population health could be greater if we shifted some resources we now devote to screening to developing, testing, and implementing alternative approaches to preventing the important threats to population health. There needs to be a wider discussion about these issues with the public.