Diagnosis of tuberculosis is mainly based on clinical features, histopathology, demonstration of acid fast bacilli (AFB) and isolation of Mycobacterium tuberculosis from the clinical specimens. These techniques have limitations of speed, sensitivity and specificity. During the last two decades several rapid techniques for detection of early growth (5-14 days as compared to 2-8 wk with conventional methods) have been described which can help in obtaining the culture and sensitivity reports relatively early. Prominent among such methods are BACTEC, mycobacterial growth indicator tuber (MGIT), Septi-chek, MB/ BacT systems. This growth can be established by rapid methods based on lipid analysis and specific gene probes, PCR-RFLP methods and ribosomal RNA sequencing. Advances in knowledge about genetic structure of tubercle bacillus helped develop gene probes and gene amplification methods for identification and detection of tubercle bacillus, from culture or directly in clinical specimens and molecular detection of drug resistance. While the gene probes can help in rapid identification of isolates, gene amplification methods (PCR as well as isothermal) developed for diagnosis of tuberculosis are demonstrably highly sensitive specially in culture negative specimens from different paucibacillary forms of disease. With these molecular methods drug resistant mutants for drugs like rifampicin can be detected with reasonable certainty within hours. These gene probes, gene amplification methods and in situ approaches offer unparalleled capability to enhance the diagnosis of tuberculosis in near future.