The review of the literature and analysis of the authors’ own data are devoted to diagnosis of neurosyphilis (NS). This disease is a severe form of syphilis and often leads to disability and even death. NA is an interdisciplinary problem which should involve different specialists. Since clinical course of the disease is often non-specific, laboratory data as the most objective approach for management of NS patients should be considered for NS diagnosis. In this regard, numerous studies are conducted abroad and in Russia in recent years in order to optimize clinical and laboratory diagnosis of NS. A group of specialists from the Moscow Center for Dermatovenereology has conducted comparative clinical and laboratory studies of routine and modern laboratory methods and approaches to the analysis of cerebrospinal fluid including VDRL, immune chips, as well as ITPA-index. Considering the most interesting scientific and applied developments of foreign and Russian colleagues, as well as own results, the authors concluded that serum-liquor ratio in paired samples (CSF — serum) is the most perspective examination. This approach is useful to obtain reliable data about central nervous system involvement and effectiveness of therapeutic effect on basis of normalization of cerebrospinal fluid.