Tubercle bacillus has remarkable ability to persist in the human host and has caused latent infection in one third of the world population. The current tuberculosis (TB) chemotherapy while effective in killing growing bacilli is largely ineffective in killing persistent or dormant bacilli, leading to prolonged therapy. There is considerable recent interest to study mechanisms of persistence and dormancy in mycobacteria. Meanwhile, there is also confusion about the use of terminology of dormant and persistent bacilli. Different models of mycobacterial persistence have been established. Various mycobacterial factors have recently been identified that may be involved in persistence or dormancy and resuscitation of dormant organisms. The phenotypic resistance to antituberculosis drugs in persistent and dormant bacilli presents a major challenge for effective control of the disease. The host immune system is critical in controlling latent TB infection from reactivation. A recent interesting observation is the reactivation of latent TB infection by anti-TNF-alpha antibody used as a treatment for rheumatoid arthritis and Crohn's disease. The role of psychoneuroendocrinological factors in TB, which is often ignored in the era of modern chemotherapy but could be important for controlling latent infection, is also briefly reviewed. There is recent interest to develop new TB drugs that target persistent and dormant bacilli and also immunotherapeutic agents that enhance chemotherapy and better control latent infection. The complex interaction between the bacteria, drugs, host and the environment underscores the need for a combined approach that incorporates chemotherapy, immunotherapeutic agents, improved socioeconomic, nutritional and even conducive psychological factors for more effective control of TB and latent TB.