Infectious diseases are the leading cause of death among children and adolescents globally, and one of the primary causes of mortality in adults. Vaccines stimulate the human body’s natural immune system to recognize and remember pathogens, so when they are later encountered, they can be more easily destroyed and disease can be lessened or prevented. They are known to be the safest, most effective way to prevent infectious diseases, and they have enabled the worldwide eradication of many devastating diseases like polio and smallpox. The recent outbreak of Zaire Ebola virus in West Africa altered the classical paradigm of vaccine development and that for emerging infectious diseases (EIDs) in general. In this paper, the precepts of vaccine discovery and advancement through pre-clinical and clinical assessment are discussed in the context of the recent Ebola virus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Zika virus outbreaks. The development of safe and effective vaccines to protect against global infectious diseases, enteric diseases, and other neglected diseases of the developing world is of critical public health importance. Development and availability of such vaccines, particularly for use in the developing countries most affected by these diseases, will benefit U.S. and global health.