Considered for years as sterile, respiratory tract contains very variable bacterial microbiome. Driven by next generation sequencing techniques, microbiome analyses allow a better understanding of viral infection pathophysiology, in terms of incidence and lethality. After a short reminder of microbiome characterization methods, this review will describe its impact on adaptive and innate immunity of the infected host. Studied by viral challenges after antibiotic administration, microbiome depletion has an important impact on clinical outcome of the host. Patient's management and therapeutic choices could exploit results of this field of research, using microbiome characteristics as prognostic biomarkers. Numerous immunologic pathways are impacted by modification of the microbiome and its restoration, using probiotic or innovative molecules could confer better clinical prognostic of viral respiratory diseases.