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The lungs of healthy humans were previously believed to be sterile, based on results of classical, culture-based studies. Therefore, the lungs were not included in the National Institutes of Health’s initial Human Microbiome Project. However, recent culture- independent methods demonstrate that the lungs of healthy humans are inhabited by communities of bacteria that are very few in number but composed of diverse types of bacteria. On the other hand, at the present time, there are signifi cant methodologic and technical hurdles that must be addressed in ongoing investigations. Quantitative and/or qualitative changes in the lung microbiome may be contributed to disease occurrence, progression and exacerbations in a number of pulmonary diseases. Knowledge of the composition and immunological effects of the lung microbiome will likely provide important pathogenic insights in diseases such as especially cystic fi brosis, bronchiectasis, asthma and chronic obstructive pulmonary disease. We anticipate that multicenter studies involving large cohorts in the future will contribute to our knowledge and understanding of the lung microbiome.