Intra-BM injection (IBMI) has been used clinically as a technique to deliver medications, blood products and fluids to critically ill children and war-wounded soldiers. Interest in IBMI has now been renewed in the setting of hematopoietic cell transplantation, in particular when umbilical cord blood is the graft source. Clinical studies have not yet unequivocally shown improvement in hematopoietic recovery. However, most intriguing is the observation, both in the clinical setting and in murine models, that the IBMI delivery of hematopoietic grafts and lymphocytes may reduce in the risk of acute GVHD. The underlying mechanism of the reduced risk of GVHD requires further investigation. In this study, we review the rationale as well as the clinical and pre-clinical data that support the study of IBMI as a method to deliver hematopoietic cells.