Multiple sclerosis (MS) is an autoimmune disease of the human central nervous system (CNS) of unknown etiology that causes demyelination and associated tissue injury. Trafficking of inflammatory T cells into the CNS is a crucial event in the pathogenesis of MS, a process in which chemokines and their receptors have been demonstrated to play an important role. Chemokines are key mediators of inflammation and have major effects on migration of cells to the sites of inflammation as well as activation of recruited and resident CNS cells. This paper summarizes recent and new information about the expression and function of elements of the chemokine system in MS and its animal model experimental allergic encephalomyelitis. Analysis of the chemokine system provides insights into mechanisms of CNS inflammatory reactions and may lead to new targets of therapeutic intervention in MS.