Chemokines are small chemotactic cytokines involved in numerous biologic and pathologic processes. They are important mediators of leukocyte trafficking, development of inflammation, tumor metastasis and immune cell differentiation. Inflammation in the CNS develops in a unique manner that is partially due to the existence of the blood–brain barrier. All inflammatory cells migrate to the CNS through the blood–brain barrier in a multistep process of cell–cell interactions. The key players involved in this transmigration are adhesion molecules and chemokines. Substantial knowledge about involvement of chemokines and their receptors in the immune-mediated CNS inflammation has been accumulated in recent years. Initially, these studies involved animal models of neuroinflammation, however, later studies on human diseases were performed. Results obtained in these experiments confirmed the significant role of the chemokine system in certain pathologies. These observations suggest that antichemokine strategies may be beneficial in the treatment of immune-mediated CNS inflammation.