A new article published in Hemodialysis International reported that pain management in end stage renal disease (ESRD) patients is a complex and challenging. It was stated that pain is prevalent in more than 50% of hemodialysis patients, while approximately 75% of these patients are treated ineffectively due to its poor recognition by providers. A good history and intensity assessment using visual analog scale are the initial steps in the management of pain followed by involvement of palliative care, patient and family counseling, discussion of treatment options, and correction of reversible causes. Further, the article discussed that first line therapy should be conservative management such as exercise, massage, heat/cold therapy, acupuncture, meditation, distraction, music therapy, and cognitive behavioral therapy. Subsequently, analgesics are introduced according to WHO guidelines (by the mouth, by the clock, by the ladder, for the individual, and attention to detail) using three-step analgesic ladder model. Neuropathic pain can be controlled by gabapentin and pregabalin. Finally, substitution/addition of opioid analgesics are indicated if pain control is not optimal. Commonly used opioids in ESRD patients are tramadol, oxycodone, hydromorphone, fentanyl, methadone, and buprenorphine. While, methadone, fentanyl, and buprenorphine are the ideal analgesics in ESRD. On the other hand, complex pain syndrome requires multidrug analgesic regimen comprising opioids, non-opioids, and adjuvant medication, which should be individualized to the patient to achieve adequate pain control.