Leprosy is an ancient disease, which was treated by local application of chaulmoogra/hydnocarpus oil during prechemotherapeutic era. Since 1940, dapsone was the only chemotherapeutic agent used for treatment of leprosy for about three decades. Prolonged, interrupted and inadequate use of dapsone monotherapy, leads to development of dapsone-resistant cases. Usefulness of clofazimine was known in 1962. Introduction of rifampicin--a powerful bactericidal drug in 1970 has opened the avenues of multidrug therapy to treat leprosy. Multidrug therapy recommended by World Health Organisation came into practice after 1982. The regimen followed now is for duration of 6 months in paucibacillary and for the duration of 12 months in multibacillary cases. It is proven to be safe and effective. Multidrug therapy for leprosy cases is available in the form of blister calender packs and is available free of cost at all government health facilities. Although more new drugs such as ofloxacin, minocyclin, clarithromycin, etc, are known now but they are used as alternative drugs if a component of combination in multidrug therapy becomes contra-indicated. This article brings the details of various drugs used under multidrug therapy, their characteristics, side-effects, regimens and alternative drugs available for treating leprosy.