Vaccines are the most successful and cost-effective medical interventions available to fight infectious diseases. They consist of biological preparations that are capable of stimulating the immune system to confer protective immunity against a particular harmful pathogen/agent. Vaccine design and development have evolved through the years. Early vaccines were obtained with little implementation of technology and in the absence of fundamental knowledge, representing a pure feat of human ingenuity. In contrast, modern vaccine development takes advantage of advances in technology and in our enhanced understanding of the immune system and host-pathogen interactions. Moreover, vaccine design has found novel applications beyond the prophylactic arena and there is an increasing interest in designing vaccines to treat human ailments like cancer and chronic inflammatory diseases. In this chapter, we focus on prophylactic vaccines against infectious diseases, providing an overview on immunology principles underlying immunization and on how vaccines work and are designed.