This is a tale of pathogenic viruses and the men and women who tried to fight them through the creation of vaccines. The story of vaccines is complicated as it requires an understanding of both viral biology and human immunology, and that knowledge only slowly developed in the twentieth century. Science tries to be rational, but it isn’t always linear. Sometimes critical advances stem from seemingly random or chance occurrences rather than thoughtful and cogent planning. A successful scientific story often includes a chaotic mixture of perceptive intelligence, perseverance, unrelenting effort, and occasionally good luck. Imagine the global body of scientific knowledge as an enormous and growing virtual book that contains the sum of all we’ve learned and discovered. Many disparate types of research, often from different countries and continents, will weave and intertwine as the tale unfolds. Multiple investigators pursue their individual plots without knowing how their efforts will contribute to the overall tome. Some scientists will write whole chapters in the book of knowledge whereas others may contribute only a few lines or words. And as in any book, some characters are heroes, and some are villains. Yet from these combined efforts ultimately emerges clarity, understanding, and a story that never before existed in the minds of men. Virologists, immunologists, molecular biologists, physicians, clinical trial volunteers, and many others all made important contributions to this tale, and we will explore vaccination from its crude beginnings to the sophisticated molecular vaccines that fought the COVID-19 epidemic. The chronicle of vaccines isn’t finished yet, but we know the ending we seek, the conquest of all harmful human viruses through vaccination.