Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by altered immune tolerance to specific proteins leading to a selective destruction of insulin-producing beta cells in genetically predisposed individuals. T1D is likely to be triggered by environmental factors, including virus infections in genetically predisposed individuals. Rotaviruses are the main cause of severe diarrhea among children worldwide, but they seem to have a role also in T1D induction. Epidemiological data may be consistent with a similar hypothesis. Mechanisms hypothesized include molecular mimicry, bystander activation (with or without epitope spreading), and viral persistence. In this review the authors analyze the factors accounting for rotavirus ability to prime islet autoimmunity and cause T1D. A thorough comprehension of their potential pathogenetic mechanisms may allow preventive strategies to be designed.