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Biochemical, serological and microbiological methods have been used to dissect pathogens and identify the components useful for vaccine development. Although successful in many cases, this approach is time-consuming and fails when the pathogens cannot be cultivated in vitro, or when the most abundant antigens are variable in sequence. Now genomic approaches allow prediction of all antigens, independent of their abundance and immunogenicity during infection, without the need to grow the pathogen in vitro. This allows vaccine development using non-conventional antigens and exploiting non-conventional arms of the immune system. Many vaccines impossible to develop so far will become a reality. Since the process of vaccine discovery starts in silico using the genetic information rather than the pathogen itself, this novel process can be named reverse vaccinology.