CXCL12, also known as SDF-1 (stromal cell derived factor-1) is a small protein that belongs to the chemokine family, whose members have a crucial role in directing cell migration. CXCL12 has an essential role in neural and vascular development, hematopoiesis and in immunity. It acts through two receptors, CXCR4 and CXCR7. While the former is a classic G protein-coupled transmembrane chemokine receptor, the latter primarily function as a scavenger of CXCL12. CXCL12 has been considered as a standard pro-inflammatory molecule for a long time, as it attracts leukocytes to inflammatory sites and contributes to their activation. However, recent findings indicate that this chemokine has the opposite role in neuroinflammation. In this review, basic data about molecular and functional properties of CXCL12 are presented, while its role in CNS autoimmunity is addressed in details.