Noroviruses and sapoviruses are common causes of gastroenteritis and infectious diarrhea. Although these viruses are typically of short duration in healthy individuals, immunocompromised organ transplant recipients can develop chronic, relapsing symptoms with grave outcomes. We discuss a unique case of chronic norovirus infection with subsequent sapovirus infection in a kidney transplant recipient. Relief of norovirus symptoms occurred after the reduction of immunosuppression and treatment with nitazoxanide. Subsequently, a superimposed sapovirus infection developed. Patient developed renal transplant rejection due to reduction of immunosuppression. Findings from this case study suggest that norovirus and sapovirus are associated with chronic, relapsing symptoms and significant morbidity in immunocompromised renal transplant patients and that reduction of immunosuppression in order to overcome infection risks allograft rejection. Early detection and management are essential to reduce morbidity associated with these viruses among immunocompromised transplant recipients.