Due to the effectiveness of vaccines some particularly threatening infectious diseases have become rare; however, vaccines are meanwhile the victims of their own success. Due to insufficient compliance and inadequate vaccination rates, there is a danger that the effectiveness of vaccination as a preventive measure will continuously disappear. In 2019 the World Health Organization classified doubts on the effectiveness of vaccines as 1 of the 10 greatest dangers to health worldwide. This article discusses important questions on vaccinations and vaccines as well as their effects in the interplay with the immune system. The following topics are covered: comparison of naturally acquired immunity and that acquired by vaccination, factors that necessitate a refresher vaccination, the role of herd immunity, prerequisites for successful eradication of a disease, influence of various T cells on the effect of vaccination, the role of immunologic memory, factors that influence protection by vaccination, vaccinations in cases of immunodeficiency, the potential and areas of implementation of passive immunization. In view of the corona pandemic and the running vaccination campaign, it must be hoped that this triggers a general renaissance of vaccinations against infectious diseases.