The continuing global epidemic of tuberculosis, the increasing rate of multidrug resistant (MDR) tuberculosis and the more recent emergence of extensively drug resistant (XDR) tuberculosis are great causes for concern. A major international effort is currently underway to optimize current drug therapies and to discover new drugs that are active against these organisms. This effort has created a pipeline of new candidate drugs at various stages of preclinical and early clinical evaluations. Major challenges still exist, however, varying from the standardization and application of current animal models and their application to drug discovery and characterization to the fact that our knowledge about the basic biology of the MDR and XDR strains of Mycobacterium tuberculosis is minimal at best.