Cryptosporidium is an intracellular protozoa that can cause gastroenteritis in humans. In immunocompromised hosts, infection can be severe, leading to life-threatening persistent diarrhea. There is limited experience in treating this infection in solid organ transplants. Although newer drugs active against Cryptosporidium exist, they are only licensed in the USA for treatment of immunocompetent hosts. Here we describe a seven-year-old renal transplant recipient with severe cryptosporidiosis. He had a protracted course of diarrhea of up to 2 L/day. He was successfully managed with combination antimicrobial therapy including nitazoxanide, paromomycin, and azithromycin. In conjunction with this regimen, he had a reduction in immunosuppression and complete bowel rest. His stool pattern normalized in four weeks and he has had no recurrence after six months of follow up.