Patients with primary immunodeficiencies are prone to develop enteropathy of unknown pathogenesis. We hypothesize that ineffective clearance of gastrointestinal pathogens, particularly viruses, in combination with defective immune regulation may cause inflammatory enteropathy in certain immunodeficient hosts. We reviewed publications related to prolonged enteric viral infection, immunodeficiency, and the subsequent development of inflammatory enteropathy. Prolonged infection with especially enteroviral infections was reported more often in immunocompromised hosts than in healthy individuals. Protracted enteric viral shedding was not always associated with the presence or duration of gastrointestinal symptoms. The development of immunodeficiency-associated enteropathy after prolonged viral infections was described in sporadic cases. Clinical consequences of viral gut infections in immunocompromised hosts comprise isolation issues and supportive care. Prospective studies in cohorts of immunodeficient patients are required to study the impact of prolonged enteric viral replication with respect to the pathogenesis of non-infectious enteropathy.