The introduction of culture-independent techniques for the microbiological analysis of respiratory samples has confirmed that the respiratory system hosts a large number of microorganisms, which include a wide range of bacteria. The regular exposure to tobacco smoke changes the microbiome in healthy smokers, first in the oropharynx, increasing the presence of a restricted number of genera which attain high relative abundance, a pattern that may be considered as dysbiosis. In chronic obstructive pulmonary disease (COPD), microbiome analyses of sputum samples have demonstrated an important decline in bacterial diversity, with a change to a restricted flora with an overrepresentation of the Proteobacteria phylum, which include most of the bacteria commonly considered as potentially pathogenic microorganisms, paralleled by a decline in the relative abundance of microorganisms part of the Firmicutes phylum. In exacerbations, specific bacteria overrepresented in microbiome analyses and potentially causal of the acute episode may not be recovered by sputum culture, while colonizing microorganisms grow easily, in spite that their relative abundance have not changed from previous stability. This situation has been described in patients showing chronic colonization by Pseudomonas aeruginosa, who suffer from exacerbations that in most cases are due to other PPMs, in spite of the persistence of positive cultures for the colonizing Pseudomonas strains.Interaction between different microorganisms can be addressed through microbiome analyses, and functional metagenomics, that describes the genomic potential of the community, has shown that, in spite that the bronchial microbiome as a whole may not change significantly, clear changes in carbohydrate metabolism, cancer, cell growth and death, transport and catabolism pathways often appear during exacerbations. These functional changes may be important because through them the resident community as a whole show its power to modify important metabolic patterns.