HSC mobilization is an essential homeostatic process during inflammation and for the maintenance of hematopoietic progenitors. It has been exploited for the therapeutic application of HSC transplantation. Recent evidence suggests that leukemic cells share surface molecules in common with stem cells and may be mobilized under similar conditions. This effect could be used for therapeutic interventions. In this review, we will provide evidence showing that leukemia cells and stem cells traffic similarly and may share a common niche. Studies are discussed comparing and contrasting the mechanism of normal stem cells and leukemic cell mobilization through the CXCR4/CXCL12 axis and other key intermediaries.