Compelling evidence has been accumulating recently implicating disruption of CXCR4/CXCL12 signaling as a key step in the mobilization of hematopoietic stem and progenitor cells (HSPCs) induced by G-CSF and other agents. This knowledge formed the rationale for the clinical development and ultimate FDA approval of a specific CXCR4 antagonist, AMD3100, for the mobilization of HSPCs in patients with non-Hodgkin lymphoma and multiple myeloma when given in combination of G-CSF.