Mouse cDNA CXCL12 was initially cloned from a bone marrow stromal cell library. CXCL12 and its receptor CXCR4 are involved in the regulation of migration, survival, and development of multiple cell types, including human hematopoietic CD34+/CD38-/low and stromal STRO-1+ stem cells. Stress-induced modulations in CXCL12 and CXCR4 levels participate in recruitment of immature and maturing leukocytes from the BM reservoir to damaged organs as part of the host defense and repair mechanism. In addition, CXCL12 and CXCR4 are key regulators of the stem cell mobilization process to ischemic tissues and therefore crucial for tissue repair. The CXCL12/CXCR4 system is involved in the establishment of organ metastasis in different cancers. Cancer stem cells (CSCs), a small subset of cancer cells, constitute a reservoir of self-sustaining cells with the ability to maintain tumor growth. Most of them express the CXCR4 receptor and respond to a chemotactic gradient of CXCL12, suggesting that CSCs probably represent a subpopulation capable of initiating metastasis. Additional data has shown that CXCL12 binds to a second receptor, CXCR7. This receptor is expressed in endothelial cells and is associated with tumors. CXCL12/CXCR4/CXCR7 axis activation seems to regulate the metastatic process.