For a number of years, a major effort has been put into the identification of candidate molecules for inclusion in a novel vaccine against tuberculosis. Various techniques have been exploited and have resulted in the identification of immunologically important antigens such as the immunodominant antigens ESAT-6 and antigen 85A/B. Today, the availability of the total nucleotide sequence of the Mycobacterium tuberculosis genome enables a post-genomic antigen discovery approach based on denotation and screening of complete protein families containing immunodominant molecules. One group of genes sharing properties with ESAT-6 constitute what has been called the esat-6 gene family. The genes have 10-35% homology to esat-6, are approximately the same size and share genomic organization. The data accumulated so far demonstrate that these molecules are immunodominant antigens strongly recognized in human TB patients and with the potential for a novel TB vaccine.