Epstein Barr virus (EBV) was discovered 60 years ago as the first candidate human tumor virus. Since then, we have realized that this human γ-herpesvirus establishes persistent infection in the majority of adult humans but fortunately causes EBV associated diseases only in a few individuals. This is an incredible success story of the human immune system, which controls EBV infection and its transforming capacity for decades after initial virus encounter. A better understanding of this immune control would not only benefit patients with EBV associated malignancies but could also provide clues on how to establish such a potent, mostly cell-mediated immune control against other pathogens and tumors. However, the functional relevance of EBV specific immune responses can only be addressed in vivo and mice with reconstituted human immune system components (humanized mice) constitute a small animal model that can be infected with EBV, recapitulates some aspects of virus associated tumorigenesis, and mounts mostly cell-mediated immune responses against EBV. This chapter will summarize the insights into EBV immunobiology that have already been gained in humanized mouse models and provide an outlook into promising future avenues to further characterize EBV infection, immune control, and associated pathologies in vivo.