New results from the laboratory of Camilla Forsberg at the Institute for the Biology of Stem Cells, University of Santa Cruz, California are beginning to unravel the mechanisms by which transplanted haematopoietic stem cells (HSCs) localise to the bone marrow niche. HSC transplants are a common treatment for various illnesses including certain blood cancers and their correct localisation is critical to the successful function of grafted cells. In their study, Smith-Berdan et al. investigated the guidance molecule Robo4 and discovered its role as a HSC-specific adhesion molecule by facilitating the adhesion of HSCs to the bone marrow niche. They demonstrate that HSCs lacking Robo4 have reduced capacity to localise within the bone marrow following transplantation, drastically reducing long term reconstitution. They demonstrate that Robo4 exerts its effects in cooperation with the Cxcr4 protein, and that inhibition of both these proteins mediates HSC mobilisation. The identification of putative therapeutic targets in HSC transplantation therapy will no doubt lead to greater success of this strategy by enabling more specific integration of grafted cells.