Patients with end-stage-renal disease (ESRD) experience a high cardiovascular mortality and cardiovascular risk factors such as obesity, hyperlipidemia and hypertension are very common. Recent epidemiological research has revealed that the association between mortality and traditional cardiovascular risk factors has been altered and inverted in ESRD patients in a sense that a low bodymass-index, a low blood pressure or low plasma cholesterol concentrations are associated with an increased mortality. In addition, low plasma creatinine, homocysteine, uric acid, advanced glycation end products, leptin and adiponectin concentrations are indicators of a high mortality instead of the lower mortality seen in the normal population. These findings have been referred to as reverse epidemiology in the literature and the underlying causes are multifactorial comprising the malnutritioninflammation-syndrome, timing of competitive risk factors, altered pathophysiology and the impact of multiple selection biases of the studies. In the presence of reverse epidemiology, the approach to the patients and the definition of target values for therapy are difficult. In this article an attempt is made to enlighten the concept of reverse epidemiology and to review the current available literature.