Clinical prediction rules (CPRs) are important tools in the development of an evidence-based, personalized medical system. This article compares CPRs to other medical information tools, giving solvent examples of their clinical application and potential to increase efficacy and efficiency, as well as their utility in drug development. The primary focus is on the potential of CPRs to define the most effective level of generalization, predictably and reproducibly identifying homogenous groups of subjects (based on outcome) in heterogeneous and undifferentiated trial populations. This potential can be met if CPR construction integrates three elements: the identification of variables both within and outside the disorder that affect outcome and the mapping of relevant human physiome types based upon identifiable trait and reactionary patterns.