Despite advances in dialysis treatment, pruritus remains a common and distressing manifestation of chronic renal failure. Two-thirds of patients on maintenance hemodialysis experience persistent itching, however, the etiology of this condition is unknown. Although pruritic patients have higher serum levels of parathyroid hormone (PTH) than nonpruritic patients, subsequent studies do not support a role for PTH as a peripheral itch mediator. Experimental itching induced by intracutaneous histamine injections is significantly stronger in patients with uremic itching, indicating an enhanced sensitivity to pruritogens in these patients. Immunohistochemistry of skin nerve fibers has shown conflicting results and the innervation pattern of uremic skin clearly needs further elucidation. The possibility of uremic itching being a neuropathic manifestation awaits future investigations.