ABSTRACT The studies on the interplay between β-herpesviruses (CMV, human herpes viruses 6 and 7) and fungi in immunocompromised hosts, have demonstrated that a detailed knowledge of the interaction between the host and the above infectious agents may have a significant clinical relevance. β-herpesviruses may directly be associated to different pathological conditions and may indirectly be involved in the development of opportunistic infections (e.g., fungal infections), allograft rejection and decreased patient survival. Recent in vitro and in vivo studies have pointed out the importance of the microbiome, exposure to microbes and the innate immune system in determining the risk of developing infections; such microbial interactions may modulate the expression of the infection, change the microbial pathogenicity, or increase the immunosuppression.