This review provides an overview of the cellular complexity and repair mechanisms in the mammalian respiratory system, focusing on gas exchange and immunological defense functions. It highlights recent advances in understanding lung repair and regeneration, emphasizing the importance of these processes in response to acute injuries and chronic diseases. The review discusses various models of lung injury, including infectious and non-infectious acute injuries, and the role of different cell types such as airway epithelial cells, alveolar cells, and mesenchymal cells in these processes. It also explores the development of model systems and assays for studying human-specific lung diseases, including the use of primary cell cultures, induced pluripotent stem cells (iPSCs), and precision-cut lung slices. The review concludes by emphasizing the need for further research to improve our understanding of lung repair and regeneration, particularly in the context of acute and chronic lung diseases, and to develop effective therapies.This review provides an overview of the cellular complexity and repair mechanisms in the mammalian respiratory system, focusing on gas exchange and immunological defense functions. It highlights recent advances in understanding lung repair and regeneration, emphasizing the importance of these processes in response to acute injuries and chronic diseases. The review discusses various models of lung injury, including infectious and non-infectious acute injuries, and the role of different cell types such as airway epithelial cells, alveolar cells, and mesenchymal cells in these processes. It also explores the development of model systems and assays for studying human-specific lung diseases, including the use of primary cell cultures, induced pluripotent stem cells (iPSCs), and precision-cut lung slices. The review concludes by emphasizing the need for further research to improve our understanding of lung repair and regeneration, particularly in the context of acute and chronic lung diseases, and to develop effective therapies.