Since rifampicin was introduced in 1967, no novel compounds have been approved for first-line chemotherapy of tuberculosis.The inexorable rise in cases of tuberculosis worldwide, fuelled by the HIV epidemic, highlights the need for new drugs, particularly those that can shorten the duration of treatment.The World Health Organization's Stop TB strategy considers that the present high burden of tuberculosis worldwide is related not only to the spread of HIV but also to poverty and the widening gap between rich and poor in various populations, disregard for the disease and lack of appropriate healthcare services. Clinical trials of existing agents such as methoxyfluoroquinolones (e.g. gatifloxacin and moxifloxacin), which are bactericidal and potent against organisms that are not actively multiplying, are proceeding on the basis of efficacy in models of interaction and preliminary clinical data.These may provide a stopgap, but the real breakthrough will come when novel agents with potent sterilising activity are discovered. New agents will provide opportunities to intensify regimens that could be shorter in duration as well as provide more options for the eradication of multi-drug-resistant mycobacteria. © 2008 Royal College of Physicians of Edinburgh.