Recent studies have challenged the once prevalent notion that the human lungs are sterile, instead unveiling a dynamic microbial environment that interacts intricately with both the host and external factors. This review describes the distinct microbial compositions between healthy individuals and those with respiratory diseases, as well as discussing the variations in microbial composition across different disease states. We explore the crucial role of the lung microbiome in maintaining respiratory health and describe its implications in various respiratory diseases. We discuss how these microbial differences correlate with the severity and progression of respiratory diseases, including chronic obstructive pulmonary disease, cystic fibrosis, lung cancer, asthma, coronavirus disease 2019, and tuberculosis. Furthermore, we analyze the pathogenic mechanisms of the lung microbiome, as well as the associations between changes in the lung microbiome and systemic effects, including the emerging concepts of the gut-lung axis and brain-lung axis, which highlight the interconnected influence of the microbiota on lung health. This review aims to provide a comprehensive understanding of the profound impact of microbial dynamics on respiratory health and disease, suggesting new avenues for targeted diagnostic and therapeutic strategies.Copyright © 2025 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.