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This edited volume draws from health communication scholars and offers a depthful examination of the roles vaccination have played and continue to play in contributing to human, community, and transnational protection against infectious diseases. The problems associated with vaccination against infection diseases was made abundantly clear during the current pandemic of COVID-19. Vaccines were traced back to Dr. Edward Jenner in the 18th century as a tool to control smallpox in England. Today we have six different categories of vaccines (three seem most controversial today): inactivated, live-attenuated, and messenger RNA (mRNA). We examine the reasons for public reluctance and outright resistance to vaccines examining cognitive biases, communication campaign failures, politicization, misinformation, partisanship, and greed. The healthcare industry has not treated all infected people equally, especially the poor and people of color. This is true in the USA as well as abroad. In the future, we can expect more exotic infections to increase due to globalization, development, and transportation. As climate changes, humans will contact more species carrying many different bacteria and viruses. Advances in medical research have led to increases in the number of vaccinations available to control infection and outbreaks. However, the rates of vaccination have fluctuated over time. A vaccine that is not used is meaningless. To increase vaccination rates, we must learn why the public shies away from vaccinations and under what circumstances. This information will enable us to design more effective messaging and communication campaigns to maximize general resilience. An interactive partnership between providers of healthcare and their patients is a prerequisite to productive and effective vaccination campaigns