The growing importance of quality of life (QoL) measures in health care is reflected by the increased volume and rigor of published research on this topic. The ability to measure and assess patients’ experience of symptoms and functions has transformed the development of disease treatments and interventions. However, QoL remains an under-investigated issue in chronic kidney disease (CKD) and is seldom set as an outcome measure in trials in this population. In this article, we present various challenges in using patient-reported outcome (PRO) end points in CKD trials. We outline the need for additional research to examine more closely patient experiences with specific kidney disease symptoms and conditions, as well as caregiver perspectives of patients’ symptom burden and end-of-life experiences. These efforts will better guide the development or enhancement of PRO instruments that can be used in clinical trials to more effectively assess treatment benefit, and improve therapy and care. Better understanding of health-related QoL issues would enable providers to deliver more patient-centered care and improve the overall well-being of patients. Even small improvements in QoL could have a large impact on the population’s overall health and disease burden.