Until recently, epidemiology has contributed little to the understanding of kidney disease etiology. In the past, the immediate need for therapy eclipsed the longer-term need to develop preventive strategies. As a result, kidney disease epidemiology lacked sufficient institutional and financial support. These difficulties are being progressively (albeit yet incompletely) resolved. Other obstacles pertained to research methods. The need for large cohort studies to investigate a relatively uncommon outcome can be overcome by the use of alternative study designs, such as nonconcurrent prospective studies or case control studies. Unfortunately, other methodologic obstacles remain. These include (1) lack of sensitive markers of early renal insufficiency for use in general populations, (2) variations in access to end-stage renal disease therapy, (3) uncertainty regarding cause-of-death certification in persons with kidney diseases, (4) ambiguous criteria for diagnosing specific renal diseases, (5) lack of independence between risk factor assessments and kidney disease definition, (6) inconsistent risk factor assessments, and (7) inadequate conceptual models for causation of kidney failure. We suggest a global framework, including (1) defining rigorous diagnostic criteria for renal diseases, (2) conducting etiologic studies of "all-cause" end-stage renal disease, (3) systematically collecting data on risk factors for renal injury, and (5) distinguishing between initiators and promoters of renal insufficiency and between proximate and distal risk factors. These suggestions aim to foster a multidisciplinary debate on etiologic research on renal diseases. Identification of modifiable risk factors may provide a basis for effective preventive interventions.