The causative agent of tuberculosis, Mycobacterium tuberculosis, is one of the most successful of human pathogens. It can evade the host immune response and establish a persistent infection or enter a dormant state within the host which can be reactivated if the host becomes immuno-compromised. Both of these features are major obstacles to tuberculosis eradication. Dormancy and reactivation of M. tuberculosis are tightly coordinated dynamic processes involving numerous genes and their products. Molecular mechanisms underlying M. tuberculosis persistence may provide an opportunity for the discovery of effective drug targets for tuberculosis control. Here, we review the genes required for M. tuberculosis persistence and propose a regulatory network for the action of these genes using text mining. This should provide fresh insights into the persistence mechanisms of M. tuberculosis and suggest candidates for new drug targets and immune intervention.