Humanized mice, which are immunodeficient mice engrafted with human hematopoietic cells and tissues, have become essential tools for studying human immune biology. These mice support the development of a functional human immune system and allow detailed analysis of human immune functions. Recent advances in humanized mouse models have improved their ability to recapitulate human immune responses, although challenges remain, such as limited lymph node development, poor immune cell trafficking, and the presence of residual mouse innate immunity. New technologies, including knock-in and knockout approaches, have enhanced human immune system function in these models. Humanized mice have been used to study various aspects of human immunity, including hematopoiesis, immune system development, autoimmunity, infectious diseases, and tumor immunology. They have also been instrumental in HIV research, allowing the study of viral replication, immune responses, and potential therapies. Despite their utility, challenges remain in generating models with more robust human immune systems and reducing mouse innate immunity. Future developments aim to improve humanized mouse models for better translational research in immunology and disease treatment.Humanized mice, which are immunodeficient mice engrafted with human hematopoietic cells and tissues, have become essential tools for studying human immune biology. These mice support the development of a functional human immune system and allow detailed analysis of human immune functions. Recent advances in humanized mouse models have improved their ability to recapitulate human immune responses, although challenges remain, such as limited lymph node development, poor immune cell trafficking, and the presence of residual mouse innate immunity. New technologies, including knock-in and knockout approaches, have enhanced human immune system function in these models. Humanized mice have been used to study various aspects of human immunity, including hematopoiesis, immune system development, autoimmunity, infectious diseases, and tumor immunology. They have also been instrumental in HIV research, allowing the study of viral replication, immune responses, and potential therapies. Despite their utility, challenges remain in generating models with more robust human immune systems and reducing mouse innate immunity. Future developments aim to improve humanized mouse models for better translational research in immunology and disease treatment.