The paper describes the work of the Rostov-on-Don Anti-Plague Institute of the Rospotrebnadzor as the main institute for the control and prevention of cholera and the Reference Center for monitoring this infection. Based on the analysis of previous experience and the results of work in the modern period, the contribution of the Rostov-on-Don Anti-Plague Institute, as coordinator of cholera prevention measures, and the Reference Center for monitoring this infection, into ensuring the sanitary and epidemiological well-being of the country’s population for 55 years has been defined. Annually, activities to ensure external quality control of laboratory diagnostics for cholera in the Rospotrebnadzor institutions, to assess the readiness of the hospital and laboratory bases of medical facilities and centers of hygiene and epidemiology in the constituent entities of the Russian Federation, and to provide professional training for personnel are organized. New rapid molecular diagnostic tests and computer programs for conducting bioinformatics analysis of nucleotide sequences are being developed and implemented into practice. The coordinated efforts of the Reference Center with the organizations of the Rospotrebnadzor and the Ministry of Health of Russia make it possible to carry out effective proactive epidemiological surveillance of cholera in the Russian Federation.