"Humanised" mouse models have emerged over past years as powerful tools for investigating human haematopoiesis and immunity. They allowed the identification of key factors for the maintenance and function of normal and leukaemic human haematopoietic stem cells. These findings have been widely used to dissect the pathogenesis of multiple myeloid and lymphoid neoplasms, such as acute myeloid leukaemia and acute lymphoblastic leukaemia. Furthermore, these models can serve as a stepping-stone to clinical trials by testing novel drugs that target leukaemic stem cells. The investigation of human immunity in vivo is also of great interest in both the context of understanding the innate and adaptive immune system and responses to viral infections with exclusive human tropism, such as Epstein-Barr virus and human immunodeficiency virus. This review focuses on recent advances in the study of human haematopoiesis and immunity in humanised mouse models, underlining their relevance and limitations.