The lung microbiome, once thought to be sterile, has been increasingly studied as new technologies reveal its complex microbial community. The lung microbiome is mainly derived from the upper respiratory tract (URT) but has its own unique flora. The lung's clearance mechanisms, such as coughing, pulmonary macrophages, and alveolar surfactant, keep the microbiome transient and mobile, distinguishing it from other organs. While the bacteriome has been extensively studied, the mycobiome and virome remain under-researched. This review summarizes the history, composition, and function of the lung microbiome, emphasizing its interactions with the oropharyngeal and gut microbiomes and its role in innate and adaptive immune responses. It also discusses the impact of the lung microbiome on respiratory diseases such as asthma, COPD, fibrosis, bronchiectasis, and pneumonia, as well as on COVID-19 and lung cancer. The review highlights the therapeutic potential of the lung microbiome in lung diseases and identifies research gaps. The lung microbiome is dynamic, influenced by various diseases, and has a significant impact on lung development and disease progression. The lung microbiome is closely related to the oropharyngeal and gut microbiomes, with interactions between oral, gut, and lung microbes. The lung microbiome is also influenced by the gut-lung axis, which is bidirectional and affects the progression of intestinal and lung diseases. The lung microbiome is composed of bacteria, fungi, and viruses, with different species present in healthy and diseased lungs. The lung microbiome has a unique mobility characteristic, created by the clearance mechanisms of the respiratory system. The lung microbiome is also involved in immune responses, with dysbiosis affecting disease occurrence, progression, and prognosis. The lung microbiome is closely related to the oropharyngeal microbiome, with some differences in microbial composition. The gut microbiome is also closely related to the lung microbiome, with the gut-lung axis playing a significant role in disease progression. The lung microbiome has a significant impact on immune responses, with the innate immune response being the first line of defense against pathogens. The adaptive immune response involves specific cells and immunoglobulins, and is influenced by the lung microbiome. The lung microbiome is also involved in the development of lung diseases, with changes in the microbiome affecting disease progression and prognosis. The lung microbiome is a potential target for diagnosis and treatment of diseases such as cancer. The lung microbiome is a complex and dynamic community, with ongoing research aimed at understanding its role in health and disease.The lung microbiome, once thought to be sterile, has been increasingly studied as new technologies reveal its complex microbial community. The lung microbiome is mainly derived from the upper respiratory tract (URT) but has its own unique flora. The lung's clearance mechanisms, such as coughing, pulmonary macrophages, and alveolar surfactant, keep the microbiome transient and mobile, distinguishing it from other organs. While the bacteriome has been extensively studied, the mycobiome and virome remain under-researched. This review summarizes the history, composition, and function of the lung microbiome, emphasizing its interactions with the oropharyngeal and gut microbiomes and its role in innate and adaptive immune responses. It also discusses the impact of the lung microbiome on respiratory diseases such as asthma, COPD, fibrosis, bronchiectasis, and pneumonia, as well as on COVID-19 and lung cancer. The review highlights the therapeutic potential of the lung microbiome in lung diseases and identifies research gaps. The lung microbiome is dynamic, influenced by various diseases, and has a significant impact on lung development and disease progression. The lung microbiome is closely related to the oropharyngeal and gut microbiomes, with interactions between oral, gut, and lung microbes. The lung microbiome is also influenced by the gut-lung axis, which is bidirectional and affects the progression of intestinal and lung diseases. The lung microbiome is composed of bacteria, fungi, and viruses, with different species present in healthy and diseased lungs. The lung microbiome has a unique mobility characteristic, created by the clearance mechanisms of the respiratory system. The lung microbiome is also involved in immune responses, with dysbiosis affecting disease occurrence, progression, and prognosis. The lung microbiome is closely related to the oropharyngeal microbiome, with some differences in microbial composition. The gut microbiome is also closely related to the lung microbiome, with the gut-lung axis playing a significant role in disease progression. The lung microbiome has a significant impact on immune responses, with the innate immune response being the first line of defense against pathogens. The adaptive immune response involves specific cells and immunoglobulins, and is influenced by the lung microbiome. The lung microbiome is also involved in the development of lung diseases, with changes in the microbiome affecting disease progression and prognosis. The lung microbiome is a potential target for diagnosis and treatment of diseases such as cancer. The lung microbiome is a complex and dynamic community, with ongoing research aimed at understanding its role in health and disease.