Microbes are ubiquitous on the human body and comprise approximately 90% of the cells and 99% of the genes of the human supraorganism. High-throughput sequencing technology has permitted the development of culture-independent means to identify the microbiota that are unique to the various microenvironments of the body and probably contribute some function. Although the respiratory tract interfaces with the environment, the lungs were always thought to be a sterile environment - until recently, when these techniques were applied to healthy and disease states. Further, there appears to be a complex interplay between the development of the gastrointestinal and respiratory microbiota and the regulation of immune function. The contribution of this dynamic metabolic mass to respiratory disease in the newborn is unknown. This article will review emerging data from recent human and murine studies that suggest there is a microbial influence on the development of respiratory disease, but it will also highlight many of the gaps that remain in understanding the function of the respiratory microbiome. (c) 2015 S. Karger AG, Basel.