In the general population, a high body mass index (BMI; in kg/m(2)) is associated with increased cardiovascular disease and all-cause mortality. However, the effect of overweight (BMI: 25-30) or obesity (BMI: >30) in patients with chronic kidney disease (CKD) undergoing maintenance hemodialysis (MHD) is paradoxically in the opposite direction; ie, a high BMI is associated with improved survival. Although this "reverse epidemiology" of obesity or dialysis-risk-paradox is relatively consistent in MHD patients, studies in CKD patients undergoing peritoneal dialysis have yielded mixed results. Growing confusion has developed among physicians, some of whom are no longer confident about whether to treat obesity in CKD patients. A similar reverse epidemiology of obesity has been described in geriatric populations and in patients with chronic heart failure (CHF). Possible causes of the reverse epidemiology of obesity include a more stable hemodynamic status, alterations in circulating cytokines, unique neurohormonal constellations, endotoxin-lipoprotein interaction, reverse causation, survival bias, time discrepancies among competitive risk factors, and malnutrition-inflammation complex syndrome. Reverse epidemiology may have significant clinical implications in the management of dialysis, CHF, and geriatric patients, ie, populations with extraordinarily high mortality. Exploring the causes and consequences of the reverse epidemiology of obesity in dialysis patients can enhance our insights into similar paradoxes observed for other conventional risk factors, such as blood pressure and serum cholesterol and homocysteine concentrations, and in other populations such as those with CHF, advanced age, cancer, or AIDS. Weight-gaining interventional studies in dialysis patients are urgently needed to ascertain whether they can improve survival and quality of life.