Infectious diseases still remain the main cause of human premature deaths, especially in developing countries. Vaccines constitute the most cost-effective tool for prophylaxis of infectious diseases. Elucidation of the complete genomes of many bacterial pathogens has provided a new blueprint for the search of novel vaccine candidates. At the same time, it was a turning point in the development of transcriptomics and proteomics. This article concentrates on the proteomic contribution to vaccinology, pointing out relationships between genomic, transcriptomic and proteomic approaches and describing how they complement one another. It also highlights the recent proteomic techniques applied to antigen identification, their capabilities and limitations, as well as the strategies that are taken to overcome technical difficulties and to refine applied methods. Finally, some recent experimental data concerning the proteomic/immunoproteomic influence on identification of vaccine candidates to prevent human infections caused by Streptococcus spp., as well as by a major bioterrorist agent, Bacillus anthracis is presented.