Microbiota have emerged as key modulators of both the carcinogenic process and the immune response against cancer cells, and, thus, it seems to influence the efficacy of immunotherapy. While most studies have focused on analyzing the influence of gut microbiota, its composition substantially differs from that in the lung. Here, we describe how microbial life in the lungs is associated with host immune status in the lungs and, thus, how the identification of the microbial populations in the lower respiratory tract rather than in the gut might be key to understanding the lung carcinogenic process and to predict the efficacy of different treatments. Understanding the influence of lung microbiota on host immunity may identify new therapeutic targets and help to design new immunotherapy approaches to treat lung cancer. Lungs are no longer considered sterile and their microbiota are associated with lung wellness.The lung microbiome has been linked to lung carcinogenesis and establishment of lung metastasis from other primary cancers.Lung microbiota dysbiosis may modulate the risk of malignancy at multiple levels including chronic inflammation and oncogenes.Patients treated with antibiotics before/during immunotherapy present with significantly lower progression-free survival and overall survival rates compared with patients who have not received antibiotics.Profiling of the gut microbiota revealed dysbiotic signatures associated with delayed tumor outgrowth and favorable responses to immunotherapy.