Purpose of reviewNorovirus infection is an emerging chronic infection in immunocompromised hosts. The aim of this review is to discuss the pathophysiology of Norovirus infection and explore mechanistic models for chronic infection/shedder state, especially in patients with immune deficiency diseases.Recent findingsChronic Norovirus infection is increasingly associated with enteropathy associated with both primary and secondary immune deficiency diseases. There is an ongoing debate in the immune deficiency community whether it is truly a causative agent for the enteropathy or it is an innocent bystander.We describe the historic aspects of Norovirus infection, its immunology and viral structure and the basis for preventive and vaccination strategies.We also postulate in this review a disease model in immune deficiency subjects which creates a milieu for it to become a chronic and explore newer frontiers for disease modification and prevention.SummaryNorovirus is the most common cause of acute gastroenteritis in general population but the factors that lead to its persistence in patients with immune deficiency need further holistic studies. This should include host assessment, microbiome signatures, and viral pathogenic factors assessment.