The landscape of rotavirus (RV) infection has changed substantially in recent years. Autoimmune triggering has been added to clinical spectrum of this pathology, which is now known to be much broader than diarrhea. The impact of RV vaccines in these other conditions is becoming a growing field of research. The importance of host genetic background in RV susceptibility has been revealed, therefore increasing our understanding of vaccine effectiveness and giving some clues about the limited efficacy of RV vaccines in low-income settings. Also, interaction of RV with intestinal microbiota seems to play a key role in the process of infection vaccine effect. This article reviews current findings on the extraintestinal impact of RV infection and their widening clinical picture, and the recently described mechanisms of host susceptibility to infection and vaccine effectiveness. RV infection is a systemic disease with clinical and pathophysiological implications beyond the gut. We propose an "iceberg" model for this pathology with almost hidden clinical implications away from the gastrointestinal tract and eventually triggering the development of autoimmune diseases. Impact of current vaccines is being influenced by host genetics and gut microbiota interactions and these factors must be taken into account in the development of public health programs.