EBV persists life-long in >95% of the human adult population. Whereas it is perfectly immune-controlled in most infected individuals, a minority develops EBV-associated diseases, primarily malignancies of B cell and epithelial cell origin. In recent years, it has become apparent that the course of primary infection determines part of the risk to develop EBV-associated diseases. Particularly, the primary symptomatic EBV infection or IM, which is caused by exaggerated T cell responses, resulting in EBV-induced lymphocytosis, predisposes for EBV-associated diseases. The role of innate immunity in the development of IM remains unknown. Therefore, it is important to understand how the innate immune response to this virus differs between symptomatic and asymptomatic primary EBV infection. Furthermore, the efficiency of innate immune compartments might determine the outcome of primary infection and could explain why some individuals are susceptible to IM. We will discuss these aspects in this review with a focus on intrinsic immunity in EBV-infected B cells, as well as innate immune responses by DCs and NK cells, which constitute promising immune compartments for the understanding of early immune control against EBV and potential targets for EBV-specific immunotherapies.