Norovirus (NoV) is one of the most common causes of acute infectious gastroenteritis in the United States (US). The infection is typically short-lasting and self-limiting in immunocompetent hosts. Renal transplant recipients on immunosuppressive therapy are more prone to infectious gastroenteritis that can be caused by various common and opportunistic organisms. NoV infection in renal transplant patients presents as an acute diarrheal illness that may progress to a chronic infection with frequent relapses leading to adverse short-term complications (acute renal injury (AKI) and acute graft rejection from the reduction of the dose of immunosuppressive medications) and possibly long-term morbidities (malabsorption syndrome, and a decline in graft survival). The management of chronic NoV infections in renal transplant patients may be quite challenging, as no specific antiviral treatment is presently approved, and frequent adjustments of immunosuppressive therapy may be required in the setting of reduced renal clearance and the attempts to decrease immunosuppressive effects to enhance the viral clearance.Herein, the authors present a case of persistent NoV in a young female patient with a renal transplant that was associated with recurrent admissions with AKI, gross electrolyte disturbances, and significant weight loss. The relapsing NoV infection has negatively impacted the patient's quality of life and socioeconomic performance.