Leprosy is a curable disease, having been eliminated from many countries, including India. This has been possible due to the wide availability of effective and safe drugs. Treatment of leprosy has undergone considerable changes over decades, from chaulmoogra oil in 1915 to dapsone monotherapy in 1946, then eventually to multidrug therapy (MDT) in 1982. In the last two decades, reports of resistance to all first-line drugs have appeared in the literature, with the need to conduct clinical trials using newer but highly bactericidal drugs and their combinations against Mycobacterium leprae.