The history of vaccines and immunization to combat infectious diseases goes back many centuries. Chinese employed smallpox inoculation as early as the 16th century. But the scientific history of the creation of the world’s first vaccine for smallpox started with the doctor Edward Jenner in England in the 1790s. It is very difficult to estimate the global contribution of vaccines in saving lives. Reasonable estimates are in the range of around 5 million lives per year, between 1980 and 2018. In the last 200 years vaccines became a cornerstone of public health and have saved millions of human lives. More than any other public health innovation with the possible exception of improvements in sanitation and clean drinking water. Vaccines proved to be the most cost-effective means of preventing several infectious diseases, chronic diseases and some virus-related human cancers (e.g. liver and cervical cancer).The launch by WHO and its partners of the Global Polio Eradication Initiative in 1988, reduced infections by 99%, and some 5 million people have escaped paralysis. Between 2000 and 2008, measles deaths dropped worldwide by over 78% and maternal and neonatal tetanus has been eliminated in 20 of the 58 high-risk countries. During the past decades 3 major infectious diseases have attracted special attention from the international public health community: HIV (Human Immunodeficiency Virus), Malaria and Tuberculosis (TB). International campaigns and vast investment efforts have been made to develop effective vaccines against each of these infections. Today, the Global Fund Partnership (GFP) has saved 32 million lives (2018), while building resilient and sustainable systems of health. The Global Alliance for Vaccines and Immunisation (GAVI) vaccinates almost half of the world’s children, and negotiates vaccines at prices that are affordable for the poorest countries. This review contains some of the most important vaccines for the most deadly and contagious diseases, global statistics on infectious diseases and the millions of lives (mainly children) lost every year. Vaccines are now the cornerstone of global health and history shows that they have saved millions from serious disabilities and premature death.