Mouse models are of great interest for studying human respiratory pathogens. However, evolutionary species divergence has led to differences in lung structure and the immune system between humans and mice, making the study of human respiratory pathogens in mouse models a longstanding challenge. In contrast, mice with a humanized immune system can faithfully reproduce human immune responses to respiratory pathogen infection, and mice with humanized lung and lung-immune systems can be used to examine human trophic respiratory pathogen infection and the corresponding immune responses. This review summarizes the contributions and recent progress of these types of humanized mice in respiratory pathogen research.