Microscopic examination of sputum smears (search for acid-fast bacilli or AFB) is the most rapid procedure for diagnosis of contagious tuberculosis. Gene amplification is not yet reliable for direct detection of M. tuberculosis in clinical specimens that are AFB smear-negative. Culture (3 to 8 weeks on Lowenstein-Jensen medium or 1 to 4 weeks in liquid media) remains essential to identify AFB and conduct antibiotic susceptibility testing. AFB from culture can be identified in a few hours by molecular approaches with specific DNA probes. Results of susceptibility testing, even in liquid media, are not available until 2 to 4 weeks after the recovery of specimens, although mutations of the rpoB and katG 315 genes, which confer resistance to rifampin and isoniazid, can be detected within hours by molecular hybridization with specific probes fixed on strips. Immunologic tests that measure the interferon gamma produced by sensitized lymphocytes are promising tools for the diagnosis of latent tuberculosis.