Background: Chronic noncancer pain is pervasive throughout the general patient population, transcending all chronic disease states. Patients with end-stage renal disease (ESRD) present a complicated population for which medication management requires careful consideration of the pathogenesis of ESRD and intimate knowledge of pharmacology. The origin of pain must also guide treatment options. As such, the presentation of neuropathic pain in ESRD can present a challenging case. The authors aim to provide a review of available classes of medications and considerations for the treatment of neuropathic pain in ESRD. Summary: In this narrative review, the authors discuss important strategies and considerations for the treatment of neuropathic pain in ESRD, including the pathogenesis of neuropathic pain, physiological changes for consideration in ESRD patients, and disease-specific consideration for medication selection. Pharmacotherapeutic classes discussed include: anticonvulsants, antiarrhythmics, antidepressants, topicals, and opioids. Key Message: Pain management in ESRD patients requires careful assessment of drug-specific properties, accumulation, metabolism (presence of active/toxic metabolites), extraction by dialysis, and presence of drug – drug interactions. In the absence of pharmacokinetic data in ESRD patients, therapeutic window and potential risks should be factored in the decision making along with continued monitoring throughout therapy.