The emergence and spread of multidrug-resistant tuberculosis (MDR-TB), i.e. involving resistance to at least isoniazid and rifampicin, could threaten the control of TB globally. Controversy has emerged about the best way of confronting MDR-TB in settings with very limited resources. In 1999, the World Health Organization (WHO) created a working group on DOTS-Plus, an initiative exploring the programmatic feasibility and cost-effectiveness of treating MDR-TB in low-income and middle-income countries, in order to consider the management of MDR-TB under programme conditions. The challenges of implementation have proved more daunting than those of access to second-line drugs, the prices of which are dropping. Using data from the WHO/International Union Against Tuberculosis and Lung Disease surveillance project, we have grouped countries according to the proportion of TB patients completing treatment successfully and the level of MDR-TB among previously untreated patients. The resulting matrix provides a reasonable framework for deciding whether to use second-line drugs in a national programme. Countries in which the treatment success rate, i.e. the proportion of new patients who complete the scheduled treatment, irrespective of whether bacteriological cure is documented, is below 70% should give the highest priority to introducing or improving DOTS, the five-point TB control strategy recommended by WHO and the International Union Against Tuberculosis and Lung Disease. A poorly functioning programme can create MDR-TB much faster than it can be treated, even if unlimited resources are available. There is no single prescription for controlling MDR-TB but the various tools available should be applied wisely. Firstly, good DOTS and infection control; then appropriate use of second-line drug treatment. The interval between the two depends on the local context and resources. As funds are allocated to treat MDR-TB, human and financial resources should be increased to expand DOTS worldwide.