Tuberculosis (TB) remains one of the major causes of death from a single infectious agent worldwide. Of great concern for TB control is the emergence of drug resistance. Since there is no cure for some multidrug-resistant strains of Mycobacterium tuberculosis, there is concern that they may spread around the world, stressing the need for additional control measures, such as new diagnostics, better drugs for treatment, and a more effective vaccine.Pulmonary TB can be diagnosed by its symptoms, chest radiography, sputum smear microscopy and by cultivation of M. tuberculosis, which is considered as the gold standard. Recent advances in molecular biology and molecular epidemiology, and a better understanding of the molecular basis of drug resistance in TB, have provided new tools for rapid diagnosis; however, the high cost of most of these techniques, and their requirement for sophisticated equipment and skilled personnel have precluded their implementation on a routine basis, especially in low-income countries.Other nonconventional diagnostic approaches proposed include the search for biochemical markers, detection of immunological response and early detection of M. tuberculosis by methods other than colony counting.In the present article, some of these approaches will be reviewed and the feasibility for their implementation in diagnostic laboratories will be discussed.