Although vaccination has had a dramatic impact on reducing economic losses due to infectious diseases, vaccination technology has not changed dramatically over the last 200 years. However, with the advent of biotechnology and our understanding of virulence factors of infectious agents combined with our knowledge of the host immune response, we are now witnessing a revolution in the number of new agents which may potentially be controlled by vaccination, as well as the approaches being used to develop vaccines. These approaches include subunit vaccines, genetically modified live vaccines and most recently, polynucleotide vaccines. Pathogens involved in bovine respiratory disease are used as models to describe recent advances in developing new vaccines that have the potential to be safer, more economical and more efficacious. Emphasis will be placed on identification of specific proteins involved in inducing protective immunity and producing these in a mammalian expression system as subunit vaccines formulated with adjuvants. To increase the duration of immunity, the genes encoding these antigens have been introduced directly into animals as polynucleotide vaccines. The benefits and short-comings, as well as the practical problems associated (both scientific and regulatory) with eventual acceptance of these vaccines, are discussed. (C) 1999 Elsevier Science Ltd. All rights reserved.