Overweight (body mass index [BMI]=25-30 kg/m2) and obesity (BMI>30 kg/m2) have become mass phenomena with a pronounced upward trend in prevalence in most countries throughout the world and are associated with increased cardiovascular risk and poor survival. In patients with chronic kidney disease (CKD) undergoing maintenance hemodialysis an 'obesity paradox' has been consistently reported, i.e., a high BMI is incrementally associated with better survival. While this 'reverse epidemiology' of obesity is relatively consistent in maintenance hemodialysis patients, studies in peritoneal dialysis patients have yielded mixed results. A similar obesity paradox has been described in patients with chronic heart failure as well as in 20 million members of other distinct medically 'at risk' populations in the USA. Possible causes of the reverse epidemiology of obesity include: (1) time-discrepancies between the competing risks for the adverse events that are associated with overnutrition and undernutrition; (2) sequestration of uremic toxins in adipose tissue; (3) selection of a gene pool favorable to longer survival in dialysis patients during the course of CKD progression, which eliminates over 95% of the CKD population before they commence maintenance dialysis therapy; (4) a more stable hemodynamic status; (5) alterations in circulating cytokines; (6) unique neurohormonal constellations; (7) endotoxin-lipoprotein interactions; and (8) reverse causation. Examining the causes and consequences of the obesity paradox in dialysis patients can improve our understanding of similar paradoxes observed both for other conventional risk factors in chronic dialysis patients, such as blood pressure and serum cholesterol, and in other populations, such as patients with heart failure, cancer or AIDS or geriatric populations.