Physical, psychosocial, and lifestyle disturbances, along with physical and emotional symptoms, have been shown to impact the health-related quality of life (HRQOL) of those dependent on renal replacement therapy. The value of HRQOL measurement as a tool to improve clinical care has been recognized by patients, clinical investigators, and health care providers. The potential importance of HRQOL assessment lies in the additional information it provides and the impact it has on the clinical decision-making process between a patient and a physician. There remain a multitude of challenges facing renal providers who wish to incorporate HRQOL measurement to improve patient care. These challenges include the clinician's understanding of the conceptual model of HRQOL, the quality of the scientific process that contributed to the current literature on HRQOL, a willingness of the clinician to incorporate HRQOL information into clinical practice, and the logistic difficulties of collecting and applying HRQOL data in a busy practice setting. Arguably, optimizing HRQOL may be the most substantial impact the health care team will have on the person with kidney failure. In order to implement HRQOL assessment at the point of care, providers may consider using computer adaptive testing and scoring algorithms using item response theory, which will allow adequate reliability for interpretation of change among individuals. Moreover, the effective assessment and interpretation of HRQOL will be aided by continued publication of norms, outcomes of randomized controlled trials, and continued experience of investigators and clinicians.