Extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis, now known to be present in 50 countries, heighten the threat posed by untreatable and fatal human tuberculosis (TB). To combat epidemics of drug-resistant TB, it is vital to understand why some resistant strains have greater reproductive fitness — a greater propensity to spread — than drug-susceptible strains. If public health malpractice has been a more important determinant of reproductive success than genetic mechanisms, then improved diagnosis and treatment could keep the frequency of resistant strains among TB cases low in any population. Recent data suggest that national TB control programmes that use existing drugs efficiently can postpone and even reverse epidemics of multidrug-resistant TB, although the effect of such programmes on XDR strains remains largely unknown.