Multiple sclerosis is a neurodegenerative and inflammatory immune disorder in the central nervous system (CNS). Most patients show relapse-remitting clinical course. Some disease modifying medications for preventing the relapses including natalizumab (NTZ) are approved in Japan. Natalizumab (NTZ), a monoclonal antibody against α4 integrin present on the surface of lymphocytes, inhibits the binding of lymphocytes to vascular cell adhesion molecule-1 (VCAM-1) of endothelial cells and blocks the penetration of encephalitogenic T cells into the CNS. This review provides an update on the efficacy of an inhibition of relapses, adverse effects including progressive multifocal leukoencephalopathy, treatment after NTZ discontinuation, and body weight based treatment.