From the first vaccine (cowpox, developed by Edward Jenner in 1796), more than 100 years elapsed before additional vaccines for broad population use (diphtheria toxoid, tetanus toxoid, and whole cell pertussis) became available between 1920 and 1940. Then followed inactivated polio vaccine in the 1950s, and live attenuated vaccines for measles, mumps, rubella, and polio in the 1960s. In 1979, global elimination of smallpox was formally certified, with the last human case occurring in Somalia, almost 200 years after Jenner administered cowpox vaccine to James Phipps. In 2019, global elimination is tantalizingly close for maternal and neonatal tetanus and polio. Despite recent outbreaks, elimination has also been achieved at country and regional levels for measles and rubella and, if achieved globally, will offer, as it has for smallpox, large reductions in child mortality and morbidity and in health system costs. Short of elimination, it is important to define the public health impact of vaccines broadly and at the population level. These broader impacts include benefits to families flowing from prevention of long-term sequelae of infection in children, and to populations and health systems from reduced transmission of infection. Importantly, well-delivered vaccination programs will have a substantial impact by improving equality in health outcomes across populations. Broader impacts include reductions in syndromic disease beyond laboratory-proven infection (e.g., diarrhea and pneumonia), indirect reductions in disease in those not immunized (within and beyond age cohorts targeted by vaccine programs), and improvements in other health services driven by the infrastructure for vaccine delivery. Measurement of these broader impacts can be challenging and must also acknowledge the potential for trade-offs, such as replacement disease due to non-vaccine strains, as documented for pneumococcal infection. The realization of the benefits of vaccines globally for all children began with the Expanded Program on Immunization (EPI) initiated by the World Health Organization (WHO) in 1974. The EPI focused on improving coverage of six already available but grossly underutilized vaccines—diphtheria–tetanus–pertussis (DTP), polio, measles, and Bacille Calmette–Guerin (BCG). Through the EPI, estimated global coverage for 3 doses of DTP increased from around 20% to over 85%. Subsequent to the EPI, the Global Alliance for Vaccines and Immunization (GAVI), the Global Immunization Vision and Strategy (GIVS), and, most recently, the Global Vaccine Action Plan (GVAP) have aimed to improve access to additional vaccines in the poorest countries. These include Haemophilus influenzae type b (Hib), hepatitis B, pneumococcal conjugate, rotavirus, and human papillomavirus (HPV) vaccines, all introduced in high-income countries from the 1990s. In this chapter, the scope and methodological issues in measuring public health impact are reviewed, and estimates of the global public health impact of individual vaccines in children summarized, concluding with potential future benefits to global child health from expanded maternal vaccination and vaccines under development.