The intestinal microbiota plays a crucial role in numerous physiological and pathological processes of the developmental age. The development of new investigation methods, such as next generation sequencing, has allowed a more precise characterization of the intestinal microbiota. This allowed us to deepen the complex relationship between the microbial flora and our organism. One of the many functions that emerged is the ability to modulate the host's immune system. The transplantation of hematopoietic stem cells represents a privileged setting for studying this interaction since, after the procedure, we witness the immune reconstruction starting from the donor precursors. The gut microbiota influences the development of major infectious and immune-mediated complications of transplantation and has a significant impact on patient survival. These evidences underline the possible therapeutic implications of the modulation of the intestinal microbiota. An in-depth study of the relationship between the immune system and microbiotic flora could allow us to better understand the role of the latter in other infectious or immune-mediated diseases.