A growing body of literature has shown that chronic pain is common for patients with end-stage renal disease (ESRD), is typically moderate or severe, and impacts virtually every aspect of health-related quality of life. Unfortunately, there is a lack of clinical and research focus in this area in nephrology, and pain in ESRD is undertreated. This article will review the epidemiology of chronic pain in ESRD, discuss basic principles of pain assessment and management, and highlight some of the challenges in pain management in ESRD with the hope of guiding health professionals in the effective management of pain in patients with ESRD.