Neurosyphilis (NS) is an interdisciplinary problem, in which a whole range of specialists should participate: dermatovenereologists, laboratory assistants, neuropathologists, psychiatrists, ophthalmologists, and others, depending on the disease manifestations. In order to verify the diagnosis and differentiate it from lesions of the nervous system associated with other causes, instrumental methods of examining patients should be widely used. Using instrumental methodologies is limited and the symptoms of the disease in many cases are nonspecific. NS diagnosis is based on laboratory diagnostics. In this regard, in recent years, numerous studies aimed at optimizing the clinical and laboratory diagnosis of this disease. For several years, a group of specialists carried out comparative clinical and laboratory studies, the development of immunochips for neurosyphilis diagnosis, and an assessment of the diagnostic significance of the ITPA index (serum-liquor ratio). Having analysed the most interesting scientific and applied developments of foreign and Russian colleagues, as well as the results of our own research, we came to the conclusion that the most promising, from a practical point of view, is the serum-liquor ratio in paired samples of patients with suspicion of neurosyphilis and, possibly, other forms of the disease. It seems that, with the help of this methodology, it is possible to obtain reliable data on the presence (absence) of central-nervous-system pathology in syphilis, and, after obtaining additional results, and on the effectiveness of therapeutic effects on the normalization (tendency to decrease the ITPA index) of cerebrospinal fluid.