Investigation of the lung microbiome is a relatively new field. Although the lungs were classically believed to be sterile, recently published investigations have identified microbial communities in the lungs of healthy humans. At the present time, there are significant methodologic and technical hurdles that must be addressed in ongoing investigations, including distinguishing the microbiota of the upper and lower respiratory tracts. However, characterization of the lung microbiome is likely to provide important pathogenic insights into cystic fibrosis, respiratory disease of the newborn, chronic obstructive pulmonary disease, and asthma. In addition to characterization of the lung microbiome, the microbiota of the gastrointestinal tract have profound influence on the development and maintenance of lung immunity and inflammation. Further study of gastrointestinal-respiratory interactions is likely to yield important insights into the pathogenesis of pulmonary diseases, including asthma. As this field advances over the next several years, we anticipate that studies using larger cohorts, multicenter designs, and longitudinal sampling will add to our knowledge and understanding of the lung microbiome.