Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) represent an emerging public health problem worldwide. The collision of the HIV epidemic with MDR- and XDR-TB has produced disastrous consequences for individual patients, with very high mortality rates reported in outbreaks among HIV-infected individuals. There is evidence of the importance of primary resistance among HIV-infected persons with XDR-TB, while the relevance of acquired resistance during inappropriate treatment among HIV-infected persons is uncertain, and TB case management of HIV-infected and -uninfected persons is based on similar standard practices to ensure treatment adherence. Current data show a limited geographical overlap of the XDR-TB and HIV epidemics: such data must be interpreted cautiously owing to the lack of adequate testing for both conditions. In fact, there are signs of an evolving epidemiological situation characterized by increased outbreak risk in concentrated areas owing to the extension of the HIV epidemic into areas of high MDR-TB prevalence and of the MDR-TB epidemic into areas of high HIV prevalence. There is a paucity of studies on treatment outcome among HIV-infected XDR-TB patients, and the only available report shows extremely high mortality rate and very short survival. Rapid diagnosis of TB and MDR-TB will be pivotal to reduce mortality among persons co-infected with HIV. However, while rapid diagnosis of MDR-TB is feasible with molecular assays on direct specimens, molecular approaches are still insensitive for XDR-TB diagnosis. There is speculative evidence that effective strategies for early HIV diagnosis and treatment will play a role in limiting the spread, and possibly improving the outcome of XDR-TB. Prevention is currently the mainstay of XDR-TB control in HIV communities. Strategies for infection control based on administrative procedures, environmental control and respiratory protection should be a priority for countries where both XDR-TB and HIV are prevalent. However, only the comprehensive implementation of the full Stop TB Strategy may be expected to curb the devastating impact of XDR-TB on HIV-infected persons.