The purpose of this article is to examine the socio-psychological story of vaccination prophylaxis as the means of preventing the spread of dangerous diseases, preserving public health, and analyzing elements of social response to it. The attitudes of society to vaccination measures are evident at various stages of the evolution of the health-care in various countries. The reasons for the formation of anti-vaccination movements and groups are examined: social, psychological, and cultural ones. The main anxieties and misconceptions of vaccination skeptics about the risks of vaccine prophylaxis are identified. Psychological and social determinants of the perception of vaccination as a threat to safety, as well as belief in myths and scientifically unfounded views, were found to be significant. Compulsory vaccination programs are discussed in terms of their legitimacy and effectiveness. To improve public understanding of the immunization and vaccine benefits, some methods are suggested as part of an integral policy and communication strategy. High-quality research data and a careful analysis of the socio-demographic and cultural features of vaccine skepticism should serve as the foundation to implement eventual initiatives.