Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that is initiated and maintained by continuous migration of inflammatory immune cells from the periphery into the target organ. However, in autoimmunity, migration of immune cells is not only involved in the pathogenesis but also in the down-modulation of the autoimmune attack, which is probably mediated by the infiltration of certain regulatory immune cell populations inside the affected organs. The migratory activity of both proinflammatory and regulatory leucocytes is controlled by chemokines and their receptors. Thus, targeting the directed migration of immune cells and regulating leukocyte trafficking across the blood-brain barrier (BBB) by means of modulation of chemokine signaling receptors might open up new therapeutic avenues not only for MS but also for other autoimmune diseases. In this review we summarize the chemotactic signaling pathways known to be involved in neuroinflammation to date and the viability of these pathways as targets for therapeutic strategies.