Most of the 20 million people in the US with chronic kidney disease (CKD) die before commencing dialysis. One of every five dialysis patients dies each year in the US. Although cardiovascular disease is the most common cause of death among patients with CKD, conventional cardiovascular risk factors such as hypercholesterolemia, hypertension and obesity are paradoxically associated with better survival in hemodialysis populations. Emerging data indicate the existence of this 'reverse epidemiology' in earlier stages of CKD. There are also paradoxical relationships between outcomes and race and ethnicity. For example, the survival rate of African American dialysis patients seems to be superior to that of whites on dialysis. Paradoxes-within-paradoxes have been detected among Hispanic and Asian American CKD patients. These survival paradoxes might evolve and change over the natural course of CKD progression as a result of the time differentials of competing risk factors and the overwhelming impact of malnutrition, inflammation and wasting. Reversal of the reverse epidemiology as a result of successful kidney transplantation underscores the role of nutritional status and kidney function in engendering these paradoxes. The observation of paradoxes and their reversal might lead to the formulation of new paradigms and management strategies to improve the survival of patients with CKD. Such movement away from the use of targets set on the basis of data gathered in general populations (e.g. the Framingham cohort) would be a major paradigm shift in clinical medicine and public health.