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Rotavirus remains a common cause of hospitalization for acute gastroenteritis in the developed world. In general, rotavirus gastroenteritis (RVGE) occurs in previously healthy children, but there may also be certain definable risk factors associated with development of severe disease.A systematic literature search was performed to examine data on risk factors for severe RVGE and to describe the inconsistencies which continue to emerge in this field.Although some social risk factors were identified, including socio-economic disadvantage, they are too widespread among European populations for prevention measures to be focused on certain infant groups. Physical risk factors identified include being born prematurely, having low (1.5–2.49 kg) birth weight, requirement for neonatal intensive care facilities, malnutrition, and immunodeficiency. Rotavirus infection may also exacerbate the progression or outcome of other conditions, for example, celiac disease, acquired immunodeficiency, or renal complications, thus strengthening the case for vaccination to prevent RVGE in these patient groups.Universal mass vaccination programs, which do not discriminate between populations, would seem to be the most appropriate approach to controlling the burden of rotavirus disease.