Syphilis, the disease known to mankind for thousands of years, is one of the most serious consequences of sexually transmitted infections. During pregnancy, syphilis is annually responsible for more than 300 thousand cases and neonatal deaths; and another 215 thousand babies are at risk of dying at an early age. Syphilis substantially increases the risk of HIV infection or transmission; the physical, psychological, and social consequences of syphilis considerably reduce quality of life among those infected. Late syphilis forms (tertiary, visceral, and neurosyphilis) that often develop in able-bodied people are accompanied by crippling manifestations, leading to disability and even death of patients. For thousands of years, mankind has experienced several epidemics of syphilis, from the devastating epidemic in European countries, which emerged and spread soon after the expedition of Christopher Columbus to America, to the last epidemic in Russia and the CIS countries in the mid-1990s, which was associated with the collapse of the USSR and the destruction of the Soviet prophylactic medical examination system. The current epidemiological situation in the world, contributing to the spread of infection (military conflicts, a stream of refugees, migration, mobile population groups, sports events, tourism, etc.) and hidden reservoirs of infection predetermine the persistence of the potential of epidemics of syphilis in the present time too. Prevention is one of the ways to combat the spread of infections in general and syphilis in particular. All measures to prevent infectious diseases are divided into several types: social and individual, primary, secondary, and tertiary. Their main goal is to reduce the number of cases of infection. The paper describes both the historical aspects of the prevention of syphilis and the state of prophylaxis at the present stage, including the WHO strategic plans. Thus, all available methods of prevention are one of the solutions to the problem of the incidence of syphilis.