Tuberculosis continues to be a major health problem, with more adults dying from Mycobacterium tuberculosis than any other pathogen world-wide. With the onset of the HIV epidemic and an increase in drug-resistant M. tuberculosis strains, the need for an improved vaccine has become an international priority. The recent completion of the genome sequences for two M. tuberculosis strains provides a wealth of information that can be used to design new strategies for vaccine development. The challenge comes in making rational choices from among the 4,000 genes of the most probable candidate immunogens or virulence genes.Thus, a well-designed screen is needed to reduce the number of candidates that must be tested. Presently, the most valuable role that bioinformatics can play is to provide such a screen.