The coronavirus pandemic that began in 2019 brought to the fore the presence of a significant minority of individuals who strongly oppose vaccination. This opposition is by no means recent. Ever since the very first attempts to immunize individuals, opposition has been intense in some societies. The reasons for this opposition range from religious to political to medical. Although vaccines have eliminated smallpox and largely eliminated polio and measles, opposition to vaccination persists and, in some countries, has grown stronger. A History of Vaccines and Their Opponents seeks to describe the history of this opposition as well as its changing rationale over the years and in different societies. The discussion may ultimately provide some suggestions for reducing hesitancy in the future.