Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon antibody-mediated disease of the central nervous system. Approximately 75% of patients have antibodies against aquaporin-4, a water channel expressed on astrocytes. Untreated, approximately 50% of NMOSD patients will be wheelchair users and blind, and a third will have died within 5 years of their first attack. Unlike multiple sclerosis, a progressive clinical course is very unusual and the accrual of disability is related to relapses. Aggressive treatment of attacks and highly efficient maintenance therapies to prevent attacks are therefore crucial to prevent residual disability. In this article, we review how high dose steroids and most importantly apheresis and modern therapies implicating B cell depletion, inhibition of complement and IL-6 reception are effective to change its natural history. We will emphasize the results of three recent double blind randomized controlled studies using monoclonal antibodies allowing strong hope to modify natural history of NMOSD.