Neuromyelitis optica spectrum disorder (NMOSD) with antibodies to aquaporin-4 (AQP4-IgG) is a severe autoimmune disorder of the central nervous system. Of particular clinical interest is the association of NMOSD with systemic rheumatic diseases, primarily systemic lupus erythematosus and Sjögren's syndrome. Data accumulated to date indicate that this association is not coincidental: NMOSD is detected significantly more frequently in patients with Sjögren's syndrome than in the general population, particularly in the presence of neurological symptoms. The pathogenetic basis of this overlap syndrome lies in the commonality of key immune mechanisms – the central role of interleukin-6 (IL-6), dysregulation of the B-cell pathway, permeability of the blood-brain barrier, and the phenomenon of molecular mimicry. The advent of targeted therapies has fundamentally changed treatment options: data from the SAkuraStar and SAkuraSky trials have confirmed the high efficacy of IL-6 blockade with satralizumab in preventing NMOSD relapses, with sustained results over many years. Optimal management of patients with overlap syndrome requires close collaboration between a neurologist and a rheumatologist to select a treatment capable of controlling both conditions and preventing irreversible neurological deficits.