The introduction of multi-drug therapy (MDT) by the World Health Organization in 1982 has proved to be the most important advance in the management and control of leprosy since the first use of the sulphone drugs 40 years earlier. For the first time, the number of registered leprosy cases has shown a decline from a peak of 5.37 million in 1985 to 3.1 million in February 1992. The 2 standard MDT regimens have proved simple to apply in most parts of the world, are relatively cheap, generally acceptable, and have shown remarkably few toxic side-effects. Nevertheless, difficulties have arisen in distinguishing between multibacillary and paucibacillary leprosy, especially when skin smears are of poor quality. Relapses in paucibacillary leprosy have proved difficult to distinguish from late reversal reactions. In multibacillary leprosy, the duration of treatment, 2-10 years in lepromatous leprosy, is a source of difficulty, and in addition light-skinned patients dislike the skin discolouration caused by clofazimine, for fear that their diagnosis might be discovered. The discovery that 3 different groups of drugs are highly bactericidal for the leprosy bacillus, although not so rapidly bactericidal as rifampicin, raises the possibility of having simplified, shorter, or better supervised regimens in the future as second generation MDT. These drugs include the 4-fluoroquinolones, pefloxacin, ofloxacin and sparfloxacin, the tetracycline minocycline, and the macrolide clarithromycin. Finally, in low-prevalence areas it is opportune to consider chemoprophylaxis and immunoprophylaxis for child contacts of lepromatous patients.