The modern era of vaccination was heralded with the licensure of the first 2 measles vaccines in 1963. This new era was distinct from the preceding era of vaccination for 4 main reasons. First, federal leadership in support of immunization at the local level grew. Second, immunization proponents championed the required vaccination of children as the best means of ensuring a protected population. Third, immunization proponents championed the idea that mass vaccination would not only help manage infectious diseases but also eradicate them. Fourth, the focus of local and federally supported immunization initiatives began to extend to the “mild” and “moderate” diseases of childhood (eg, measles), so-called because they were seen as less severe than previous targets of mass vaccination, such as smallpox, polio, and diphtheria. This article follows the history of measles to explore immunization successes and challenges in this modern era, because measles was the first of the mild and moderate diseases to become the target of a federally supported eradication-through-vaccination campaign, one that relied heavily on the preemptive, required vaccination of children. Its story thus epitomizes the range of political, epidemiological, cultural, and communications challenges to mass immunization in the modern era of vaccination.