Clinical prediction rules, sometimes called clinical decision rules, have proliferated in recent years. However, very few have undergone formal impact analysis, the standard of evidence to assess their impact on patient care. Without impact analysis, clinicians cannot know whether using a prediction rule will be beneficial or harmful. This paper reviews standards of evidence for developing and evaluating prediction rules; important differences between prediction rules and decision rules; how to assess the potential clinical impact of a prediction rule before translating it into a decision rule; methodologic issues critical to successful impact analysis, including defining outcome measures and estimating sample size; the importance of close collaboration between clinical investigators and practicing clinicians before, during, and after impact analysis; and the need to measure both efficacy and effectiveness when analyzing a decision rule's clinical impact. These considerations should inform future development, evaluation, and use of all clinical prediction or decision rules.