A comprehensive molecular cell atlas of the human lung was created using single-cell RNA sequencing (scRNAseq) of ~75,000 cells from lung tissue and blood. This study identified 58 distinct cell populations in the human lung, including 41 previously known cell types and 14 new ones. The atlas provides detailed gene expression profiles, anatomical locations, and molecular functions of lung cell types, as well as insights into cell-specific transcription factors and optimal markers for their identification and monitoring. It also reveals the cell targets of circulating hormones, predicts local signaling interactions, and identifies cell types affected by lung disease genes and respiratory viruses. Comparison with mouse data revealed 17 molecular types that appear to have been gained or lost during lung evolution, highlighting the plasticity of cell types during organ development and evolution. The study identified 58 molecular cell types in the human lung, including 15 epithelial, 9 endothelial, 9 stromal, and 25 immune populations. These include new cell types and subtypes, such as alveolar type 2 (AT2) cells, which play a critical role in surfactant production. The atlas also identified new cell types in the stroma, including alveolar and adventitial fibroblasts. The study further characterized immune cell residency signatures, identifying novel dendritic populations and distinguishing between lung resident, egressed, and circulating immune cells. The atlas provides optimal markers for each lung cell type and identifies transcription factors that may be key regulators in lung development and disease. It also maps the cellular focus of lung diseases, identifying cell types affected by disease genes and respiratory viruses. The study further reveals evolutionary changes in lung cell types, showing that human lung cell types have diversified significantly during mammalian evolution, with some cell types showing divergent gene expression patterns between humans and mice. The study highlights the importance of understanding lung cell types and their interactions in health and disease, providing a foundation for future research on lung development, tissue engineering, and disease mechanisms. The atlas also has implications for understanding the evolution of lung cell types and their functions, as well as for developing targeted therapies for lung diseases. The study was conducted using a combination of scRNAseq, flow cytometry, and immunohistochemistry, and involved extensive data analysis and bioinformatics methods to identify and characterize the molecular cell types in the human lung.A comprehensive molecular cell atlas of the human lung was created using single-cell RNA sequencing (scRNAseq) of ~75,000 cells from lung tissue and blood. This study identified 58 distinct cell populations in the human lung, including 41 previously known cell types and 14 new ones. The atlas provides detailed gene expression profiles, anatomical locations, and molecular functions of lung cell types, as well as insights into cell-specific transcription factors and optimal markers for their identification and monitoring. It also reveals the cell targets of circulating hormones, predicts local signaling interactions, and identifies cell types affected by lung disease genes and respiratory viruses. Comparison with mouse data revealed 17 molecular types that appear to have been gained or lost during lung evolution, highlighting the plasticity of cell types during organ development and evolution. The study identified 58 molecular cell types in the human lung, including 15 epithelial, 9 endothelial, 9 stromal, and 25 immune populations. These include new cell types and subtypes, such as alveolar type 2 (AT2) cells, which play a critical role in surfactant production. The atlas also identified new cell types in the stroma, including alveolar and adventitial fibroblasts. The study further characterized immune cell residency signatures, identifying novel dendritic populations and distinguishing between lung resident, egressed, and circulating immune cells. The atlas provides optimal markers for each lung cell type and identifies transcription factors that may be key regulators in lung development and disease. It also maps the cellular focus of lung diseases, identifying cell types affected by disease genes and respiratory viruses. The study further reveals evolutionary changes in lung cell types, showing that human lung cell types have diversified significantly during mammalian evolution, with some cell types showing divergent gene expression patterns between humans and mice. The study highlights the importance of understanding lung cell types and their interactions in health and disease, providing a foundation for future research on lung development, tissue engineering, and disease mechanisms. The atlas also has implications for understanding the evolution of lung cell types and their functions, as well as for developing targeted therapies for lung diseases. The study was conducted using a combination of scRNAseq, flow cytometry, and immunohistochemistry, and involved extensive data analysis and bioinformatics methods to identify and characterize the molecular cell types in the human lung.