Acute gastroenteritis caused by noroviruses often has a duration of 2-3 days and is characteristically self-limiting. In contrast, chronic infection caused by noroviruses in immunocompromised individuals can last from weeks to years, making clinical management difficult. The mechanisms by which noroviruses establish persistent infection, and the role of immunocompromised hosts as a reservoir for noroviruses in the general human population, are not known. However, study of this patient cohort may lead to new insights into norovirus biology and approaches to treatment.