AbstractChronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease and the third leading cause of death worldwide. Developments in next‐generation sequencing technology have improved microbiome analysis, which is increasingly recognized as an important component of disease management. Similar to the gut, the lung is a biosphere containing billions of microbial communities. The lung microbiome plays an important role in regulating and maintaining the host immune system. The microbiome composition, metabolites of microorganisms, and the interactions between the lung microbiome and the host immunity profoundly affect the occurrence, development, treatment, and prognosis of COPD. In this review, we drew comparisons between the lung microbiome of healthy individuals and that of patients with COPD. Furthermore, we summarize the intrinsic interactions between the host and the overall lung microbiome, focusing on the underlying mechanisms linking the microbiome to the host innate and adaptive immune response pathways. Finally, we discuss the possibility of using the microbiome as a biomarker to determine the stage and prognosis of COPD and the feasibility of developing a novel, safe, and effective therapeutic target.