This chapter begins with a detailed account of the molecular epidemiology of drug-resistant TB. The mechanisms of drug resistance and the molecular basis of multiple drug resistance is then presented in exhaustive detail. Potential causes of drug resistance are explained. The basic definitions of MDR-TB, XDR-TB are presented. Principles of treatment of drug-resistant TB, including the DOTS-Plus strategy are presented. Global experience in the treatment of MDR-TB and XDT-TB are presented. Treatment of latent MDR-TB is also described.