Health-related quality of life (QOL) refers to the measure of a patient's functioning, well-being, and general health perception in each of three domains: physical, psychological, and social. Along with survival and other types of clinical outcomes, patient QOL is an important indicator of the effectiveness of the medical care they receive. QOL of patients with end-stage renal disease is influenced by the disease itself and by the type of replacement therapy. Numerous studies have identified the effect of such factors as anemia, age, comorbidity, and depression on QOL. Most of these factors appear during the predialysis period, and the adequate management of some of them could influence patient outcomes. Among replacement therapies, transplantation appears to give the best QOL for large groups of patients. No conclusive data exist to prove differences in QOL between hemodialysis patients and peritoneal dialysis patients. In the case of elderly patients or those with a high degree of comorbidity, the best treatment option should be assessed in each individual case, taking all possible factors into account. Finally, it has been proven that physical and mental function are inversely correlated with the risk for hospitalization and mortality.