Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), in which inflammation develops upon leukocyte invasion into the CNS via the blood-brain barrier. α4-Integrin is an important cell adhesion molecule involved in the penetration process. Natalizumab is an α4-integrin-targeting monoclonal antibody that was recently approved for use as a disease-modifying therapy for MS in Japan. In this article, the mechanism of action, efficacy, and side effects of natalizumab will be reviewed.