The etiology of several autoimmune diseases, including multiple sclerosis (MS) is still not clarified. MS is defined as an autoimmune disease with clinical features of a chronic, inflammatory, and demyelinating autoimmune disorder, which affects the central nervous system. Phases of remission and relapse are the major course of the disease, which could be exacerbated in terms of both severity and duration. As a subfamily of the cytokines, chemokines act as chemoattractants for a wide variety of cells, including immune cells. CXCL12, which is an important member of the CXC subfamily, has been widely explored in the hematopoietic system. In the peripheral immune system, CXCL12/CXCR4 performs pleiotropic functions. CXCL12 is a highly effective chemoattractant for lymphocytes and monocytes but not neutrophils. CXCL12 is present in the cerebrospinal fluid (CSF) of patients with MS and other inflammatory neurological disorders. The aim of this study is to summarize recent findings regarding the relationship between CXCL12 and MS.