Multidrug-resistant (MDR)--and extensively drug-resistant (XDR)--forms of tuberculosis are growing public health problems. Mathematical models predict that the future of the MDR and XDR tuberculosis epidemics depends in part on the competitive fitness of drug-resistant strains. Here, recent experimental and molecular epidemiological data that illustrate how heterogeneity among drug-resistant strains of Mycobacterium tuberculosis can influence the relative fitness and transmission of this pathogen are reviewed.