The early development of the concept of immunization and the first vaccines was based mostly on courageous work of visionaries such as Edward Jenner, Louis Pasteur and Robert Koch. From those first attempts of vaccination in the 18th century, the development of vaccines was further encompassed by some of the most significant achievements in the field of immunology, molecular biology and genetics. The development of vaccines changed the picture of global health. As the most life-saving innovation in the history of medicine, vaccines have eradicated some diseases, reduced the mortality of others and prevented many types of disabilities. From the late 18th century to modern innovative, cutting-edge technologies in the vaccine research, thousands and thousands of researchers, some who caught the spotlight and some who remained anonymous within the walls of their laboratories, contributed to their safety and efficacy. The key ethical debates surrounding the vaccines revolve around several questions, such as mandatory vs. voluntary vaccination, the ethics of vaccine development and testing, informed consent regarding risks and benefits of the vaccination, and the disparities in distribution and availability. In more developed countries, the ethical issues regarding vaccination tend to focus on the rights of individuals vs. regulatory bodies. Those issues, together with the growing anti-vaccination movement and vaccine-hesitancy, have become more significant during the time of COVID-19 pandemics. This narrative review gives a summary of the most important breakthroughs in the history of vaccine development, but also focuses on the emerging problems regarding ethics and controversies surrounding the issue of vaccination during catastrophic pandemics that affected the world.