This review discusses the role of animals in respiratory research, focusing on their use in studying chronic respiratory diseases such as asthma, COPD, cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and tuberculosis. Animal models are essential for training medical professionals, evaluating toxicants, and developing inhaled medications. Species differences in respiratory tract anatomy influence their effectiveness in predicting human toxicity. Commonly used mammalian models include mice, rats, guinea pigs, and others, while zebrafish and fruit flies are used for immunological studies. The review highlights the anatomical differences between human and mammalian lungs, the characteristics of current mammalian models for chronic respiratory diseases, and the challenges in generating animal models that mimic human diseases. It also discusses the limitations of animal models and the potential for combining in silico, in vitro, and in vivo models in future drug development. The review covers the history of animal experimentation, the physiology and anatomy of the respiratory tract in different species, histological differences, and the use of healthy animals for training and toxicity testing. It also addresses the prevalence of respiratory diseases, the use of animal models for disease research, and the challenges in translating findings from animal models to humans. The review emphasizes the importance of species-specific differences in respiratory tract anatomy and physiology in the development of effective treatments for chronic respiratory diseases.This review discusses the role of animals in respiratory research, focusing on their use in studying chronic respiratory diseases such as asthma, COPD, cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and tuberculosis. Animal models are essential for training medical professionals, evaluating toxicants, and developing inhaled medications. Species differences in respiratory tract anatomy influence their effectiveness in predicting human toxicity. Commonly used mammalian models include mice, rats, guinea pigs, and others, while zebrafish and fruit flies are used for immunological studies. The review highlights the anatomical differences between human and mammalian lungs, the characteristics of current mammalian models for chronic respiratory diseases, and the challenges in generating animal models that mimic human diseases. It also discusses the limitations of animal models and the potential for combining in silico, in vitro, and in vivo models in future drug development. The review covers the history of animal experimentation, the physiology and anatomy of the respiratory tract in different species, histological differences, and the use of healthy animals for training and toxicity testing. It also addresses the prevalence of respiratory diseases, the use of animal models for disease research, and the challenges in translating findings from animal models to humans. The review emphasizes the importance of species-specific differences in respiratory tract anatomy and physiology in the development of effective treatments for chronic respiratory diseases.