Microbial pathogens have developed complex and efficient ways of counteracting and evading innate and adaptive immune mechanisms. The strategies used by pathogens determine strongly the type of immune response a vaccine should elicit and how the vaccine should be formulated. Improved knowledge of immune response mechanisms has brought successes in the development of vaccines that protect against challenging pathogens as well as vaccines that can be used in immunocompromised and elderly populations. This includes the production of highly purified antigens that provide a better reactogenicity and safety profile than some of the early whole-pathogen vaccines. Successful attempts to improve antigen purity, however, can result in weakened immunogenicity. The search for approaches to overcome this has led to new technologies, such as live vector vaccines, DNA vaccines and novel adjuvant formulations, which have been based on growing knowledge of the interplay between innate and adaptive immune systems and the central role played by antigen-presenting cells. Of these technologies, one of the most promising to date is based on the use of innovative adjuvants combined with careful antigen selection. Vaccine design has therefore become more tailored, and in turn has opened up the potential of extending its application in immunotherapies to tackle diseases such as cancer, Alzheimer disease and immune-mediated disorders.