Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are antibody-mediated inflammatory disorders that target extracellular proteins of the central nervous system (CNS). Over the past decades, significant advances in their understanding, diagnosis, and treatment have redefined their clinical and pathological paradigms. The discovery of aquaporin-4 (AQP4) antibodies revolutionized the understanding of NMOSD, recognizing astrocytopathy as the primary pathogenic process. The diagnostic criteria have evolved to incorporate AQP4 antibody testing and expanded the spectrum of disease phenotypes. The improved understanding of disease pathophysiology has facilitated the development of highly effective therapies. The identification of antibodies to myelin oligodendrocyte glycoprotein (MOG) has also been the cornerstone for establishing MOGAD as a distinct clinical entity, subsequently leading to clarification of the spectrum of associated phenotypes, the publication of consensus diagnostic criteria, and the launch of randomized controlled trials. This article reviews key insights gained into these conditions, tracing the timelines that have shaped our knowledge. It outlines the evolution of antibody assay techniques, examines their epidemiology and phenotypic presentations, and describes the predictive factors for clinical outcome. By highlighting some remarkable treatment advances, it demonstrates the rapid and impactful progresses made in this field.