The occurrence of chronic kidney disease and subsequent rate of loss of renal function are highly variable among individuals with the same underlying cause of renal injury or degree of functional impairment. Individual variability of risk is typical of complex diseases and reflects the multifactorial nature of the biologic mechanisms that are involved in the underlying disease process. The utility of the risk factor concept in developing CKD prevention and control strategies includes identifying individuals at high risk for the occurrence and progression of CKD, defining at-risk populations, elucidating potential targets for intervention, and generating explanatory hypotheses for the variable risk of CKD noted in different populations. Future application of the risk factor concept in the prevention and control of CKD will entail developing multivariate prediction equations; using spatial and temporal, as well as personal, characteristics, to define at-risk populations; identifying biomarkers for complex risk factors like race; and translating this information into testable interventions. This should include active extension of our current understanding of health care, social, and economic risk factors at both the individual and the community level.