Novel culture-independent techniques have recently demonstrated that the lower respiratory tract, historically considered sterile in health, contains diverse communities of microbes: the lung microbiome. Increasing evidence supports the concept that a distinct microbiota of the lower respiratory tract is present both in health and in various respiratory diseases, although the biological and clinical significance of these findings remains undetermined. In this article, the authors review and synthesize published reports of the lung microbiota of healthy and diseased subjects, discuss trends of microbial diversity and constitution across disease states, and look to the extrapulmonary microbiome for hypotheses and future directions for study.