The likelihood of developing many diseases is predicted by levels of risk factors. Many public health strategies have been created to apply interventions (for example, drugs, diets, exercise) intended to lower levels of these factors and thereby prevent disease. Often, these strategies are based on the interpretation of incomplete evidence for the effectiveness of the interventions. The reason this evidence is and will likely remain incomplete is explained by the policy makers' paradox. The paradox occurs when evidence for an intervention's effectiveness is obtained in persons with the highest levels of a risk factor, but the application of the intervention may have the greatest potential for reducing disease burden in persons with lower levels. Resolution of the paradox requires consideration of the type and quality of evidence, the society's time preference for risk, and the society's choice about allocation of scarce resources.