The impact of vaccination on the health of the world's peoples has been considerable. With the possible exception of clean water, no other development has had such a major effect on the reduction of mortality and on population growth. During the last 200 years, vaccination has controlled nine major diseases and has led to the eradication of one, ie smallpox. However, in many instances the exact mechanisms of successful vaccines are not fully understood. Almost all of the vaccines in use today are of three types: live attenuated micro-organisms, inactivated whole micro-organisms, or split or subunit preparations. These have different strengths and weaknesses with respect to safety and efficacy, but traditional vaccine development methodologies have not yet led to the generation of a vaccine with all the characteristics required of the ideal vaccine. Thus, the development of improved vaccines that overcome the difficulties associated with many of the currently available vaccines is a major goal of biomedical sciences. In addition, there is an urgent need for new vaccines against the many infectious agents that still cause considerable morbidity and, in some cases, mortality. As has been the case in many areas of biology, the application of recombinant DNA approaches to vaccinology has opened up whole new possibilities. The details of these and other technologies and their application to vaccine development are described in this review.