Multiple sclerosis (MS) is a chronic demyelinating disease of the human central nervous system of a still unknown etiology. The autoimmune inflammatory process is believed to be essential for the development of the disease. Several different studies have shown that chemokines and chemokine receptors are involved in the pathogenesis of MS. Chemokines can mediate the trafficking of immune cells across the blood–brain barrier, and regulate their transfer to lesion sites. Chemokines were detected in actively demyelinating lesions and were found to be elevated in the cerebrospinal fluid of patients with MS during relapse. Different pairs of chemokine receptors and their ligands seem to play a pathogenic role in MS (e.g., CXCR3 and CXCL9, CXCL10; CCR1 and CCL3, CCL4, CCL5; CCR2 and CCL2; CCR5 and CCL3, CCL4, CCL5). Interfering with the chemokine system may be an effective therapeutic approach in MS. In this review we briefly summarize the results of the previous studies and identify the most important findings in the field.