Recent findings on the etiology and pathogenesis of multiple sclerosis (MS) and neuromyelitis optica (NMO) were reviewed. As new MS-susceptibility genes, IL-7Ralpha and IL-2Ralpha genes were identified. Among environmental factors, Epstein-Barr virus, vitamin D and smoking appear to play a role in developing MS. As opposed to previous reports on the lesion heterogeneity, a recent study showed antibody-, complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in MS. Clinical trials of monoclonal antibodies demonstrated that targeting such immune molecules as CD52, CD25, VLA-4 and CD20, is therapeutically effective. Aquaporin-4 (AQP4) antibody is a diagnostically useful biomarker of NMO, and a recent study revealed severe astrocytic damage in NMO probably caused by AQP4-targeting is a pathological finding distinct from that in MS.