Uremic pruritus occurs in up to 50% of patients undergoing chronic hemodialysis. The pathogenesis of this disabling condition is unknown but likely involves multiple pathways involving the peripheral and central nervous system as well as local chemical and inflammatory mediators. Therapy has involved modification of the dialysis procedure, topical medications such as emollients, physical treatments such as ultraviolet light, and several oral medications such as antihistamines, activated charcoal, and gabapentin. Unfortunately, most of these therapies have not been subjected to rigorous clinical trials and clinical success has been variable. Two patients with disabling uremic pruritus refractory to multiple interventions are reported, who showed significant improvement in pruritus severity as assessed by a visual analog scale when they were treated with the mast cell stabilizer cromolyn sodium. Cessation of cromolyn resulted in return of pruritus, which improved with rechallenge with the medication. Cromolyn sodium may offer an alternative therapy for patients with refractory uremic pruritus, and should be subjected to a randomized placebo-controlled trial.