The discovery of highly specific auto-antibodies directed against the water channel aquaporin 4 was a quantum leap in the definition, classification and management of neuromyelitis optica (NMO). Herein, we propose an update on epidemiological, clinical and therapeutic advances in the field, underlining unmet needs. Large-scale epidemiological studies have recently provided a more precise evaluation of NMO prevalence and a better stratification regarding ethnicity and sex. New criteria have been proposed for so-called NMO spectrum disorders (NMOSD) and their relevance is currently being assessed. The identification of a new clinical entity associated to antibodies against myelin oligodendrocyte glycoprotein questions the border of NMOSD. The concept of NMOSD is opening a new era in clinical practice, allowing an easier and more homogeneous diagnosis and an increase in newly identified cases. This will facilitate clinical studies and support new therapeutic trial. Future researches should focus on the position of seronegative NMOSD and myelin oligodendrocyte glycoprotein-IgG disorders in the field and on promising strategies, including the immune tolerisation approaches, to eventually cure NMO.