Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is one of the main killers among infectious pathogens in the world and represents an important factor that sustain poverty in developing countries. Failure of the BCG vaccine to protect in endemic regions, and increasing problems with multi-drug-resistant TB calls for development of better vaccines to prevent reactivation of tuberculosis. It has been estimated that an effective post-exposure vaccine will prevent 30-40% of the TB cases. New vaccines should also prevent development of TB in HIV-infected individuals. Recent characterization of M. tuberculosis H37Rv by proteomic methods has revealed a large number of novel secreted proteins that should be investigated in mouse models for latent and slowly progressive TB. There is an important balance between control of infection and tissue destruction in TB, and M. tuberculosis has developed strategies to prevent immune-mediated sterilization. Central to this strategy is inhibition of apoptosis of macrophages. Development of novel vaccines should therefore take into consideration the effects on central markers to obtain a better picture of regulation of immunity, including FasL and Bcl-2 which are essential in regulation of apoptosis.