This chapter discusses the antibacterial treatment of leprosy infections. Antibiotic treatment is a key component of leprosy treatment, as it is vital to prevent the progression of the infection. Treatment with rifampin and other antibiotics is highly effective and cures 98% of patients with the leprosy infection. Furthermore, the relapse rate is very low, at about 1% over 5–10 years. There is little M. leprae drug resistance in leprosy and few reports of multi-drug resistance (1, 2, 3, 4, 5, 6, 7, 8). An antibiotic treatment may take months or years to produce clinical improvement, especially in patients with an initial high bacterial index (BI).