Infectious diseases continue to be the major causes of illness, disability, and death. Moreover, in recent years, new infectious agents and diseases are being identified, and some diseases that were previously considered under control have reemerged. Furthermore, antimicrobial resistance has grown rapidly in a variety of hospital as well as community acquired infections. Thus, humanity still faces big challenges in the prevention and control of infectious diseases. Vaccination, generally considered to be the most effective method of preventing infectious diseases, works by presenting a foreign antigen to the immune system to evoke an immune response. The administered antigen can either be a live,. but weakened, form of a pathogen (bacteria or virus), a killed or inactivated form of the pathogen, or a purified material such as a protein. However, no vaccine is completely safe; therefore, vaccine safety research and monitoring are necessary to minimize vaccine related harms. From the formulation point of view, the goal continues to be to improve the quality and global availability of vaccine delivery systems. This chapter provides an introduction to vaccine formulation, describes the delivery routes that are utilized, and discusses the factors that affect the safety and stability of a vaccine formulation.