The CXCR4 chemokine receptor in homing of hematopoietic progenitors, B-lymphocyte development, and progenitor recruitment to sites of ischemic tissue damage. Homing and retention of hematopoietic progenitor cells (HPCs) within the marrow microenvironment requires active migration of HPCs to distinct hematopoietic niches. CXCL12 gradients within the marrow induce firm adhesion of circulating HPCs to endothelial cells via CXCR4, followed by transmigration and homing to marrow stromal cells. Regions of hypoxia within the marrow microenvironment display high CXCL12 concentrations that attract HPCs, as indicated by the triangles on the left-hand side. Homing of circulating progenitors, such as cardiac, endothelial, or neural progenitors, to peripheral tissues for repair after ischemic injuries also requires CXCR4. Hypoxia-inducible factor-1 (HIF-1) induces expression of CXCL12 in direct proportion to reduced oxygen tension at sites of injury. As such, CXCL12 recruits CXCR4-expressing circulating progenitors to “conditional” stem cell niches for tissue repair. Early steps of B-lymphocyte development from HPCs are critically regulated by close contact with marrow stromal cells. Both early B-cell precursor (pre-pro-B cells) and end-stage B cells (plasma cells) require CXCR4 for homing to specific niches within the marrow. Other developmental stages of B cells migrate to other niches within the marrow (pro B cells), leave the marrow, and circulate through the secondary lymphatic tissues where B- and T-zone chemokines (CXCL13, CCL19, CCL21) regulate their homing. Plasma cell differentiation is associated with a coordinated switch in chemokine sensitivity with an increased sensitivity to CXCL12, which allows for plasma cell homing to the marrow.