Resistance to antituberculosis drugs has been a problem since the era of chemotherapy began. After dramatic outbreaks of multidrug-resistant tuberculosis (MDR-TB) in the early 1990s, resistance became recognized as a global problem. MDR-TB now threatens the inhabitants of countries in Europe, Asia, Africa, and the Americas. An understanding of the molecular basis of drug resistance may contribute to the development of new drugs. Management of MDR-TB relies on prompt recognition and treatment with at least 3 drugs to which an isolate is susceptible.