The ability to induce and/or monitor an immune response to a broad repertoire of epitopes universally recognized across continents and genetic backgrounds is considered a critical characteristic of an effective vaccine and diagnostic tool. Opportunities for epitope identification are expanding as the number of entirely sequenced pathogens approaches 500 and access to this data improves. The pace of vaccine design will accelerate as bioinformatics are systematically applied to whole genomes and used in combination with in vitro methods for screening and confirming epitopes. Given access to bioinformatic tools, epitope-driven diagnostic tools and both preventive and therapeutic vaccines (for infectious diseases of worldwide impact such as tuberculosis and HIV) are now within our reach. This review describes the structural basis of the bioinformatic tools for epitope prediction methods as well as the recent use of these approaches at genomic level in the development of diagnostic tools and vaccine design as example of structural bioinformatic system applied to pharmacogenomics.