Pulmonary tuberculosis (TB) has again become a global problem: it infects 2.2 
billion people world-wide, caused the deaths of over 3 million last year and 
will produce over 8 million new cases of TB this coming year. Although effective 
therapy is widely available for antibiotic susceptible strains of Mycobacterium 
tuberculosis, current drugs are relatively useless against multi-drug resistant 
infections (MDRTB). Mortality is almost complete within two years regardless of 
therapy, and in the case of co-infection with HIV/AIDS, mortality is 100% within 
a few months of diagnosis especially the M. tuberculosis strain in XDRTB. As of 
the time of this writing no new effective anti-TB drugs have been made available 
by the pharmaceutical industry and XDRTB. Because TB is an intracellular 
infection of the non-killing macrophage of the lung, any agent that is to prove 
effective must have activity against MDRTB and XDRTB strains that have been 
phagocytosed by the human macrophage. This review intents to provide cogent in 
vitro, ex vivo and in vivo evidence that supports the use of a variety of 
commonly available phenothiazines for the therapy of MDRTB and XDRTB, especially 
when the prognosis of the infection is poor and the use of the recommend agents 
can take place along lines of "compassionate therapy". In addition, we will 
describe the macrophage assay as indispensable when an agent is to be further 
studied for its effectiveness as an anti-TB drug. In vitro studies if not 
complemented by ex vivo studies will for the most part be dead-ended since few 
agents that have activity in vitro have any activity against phagocytosed M. 
tuberculosis.