Infections with Mycobacterium tuberculosis remain a major cause of disease and death in humans. Among the factors that contribute to M. tuberculosis's success as a pathogen is its ability to withstand potentially bactericidal host defences and to resist elimination by an activated immune system. This resistance to killing by the host is in part due to the low permeability of the mycobacterial cell envelope for many toxic molecules. In addition, it depends upon the detoxification of reactive oxygen and reactive nitrogen molecules produced by the host, the repair of the damage these molecules cause and maintenance of a neutral intrabacterial pH within acidic environments. The latter three mechanisms are the focus of this review.