T-cell migration into the central nervous system (CNS) is a critical element in infiammatory and autoimmune diseases of the nervous tissue. Although several components involved in this process have been identified, we still lack a complete understanding of the initiation of CNS immune reactivity and T-cell recruitment into the CNS. Elucidating the pathways that promote T-cell migration and recruitment into the CNS is therefore necessary in order to gain an understanding of CNS immune reactivity and to design novel immune therapies that interfere with infiammatory and autoimmune diseases of the CNS.