The World Health Organization estimates that there are 650,000 prevalent cases of multidrug-resistant (MDR) tuberculosis (TB) globally, and since children (<15 years of age) constitute up to 20 % of the TB caseload in high-burden settings, the number of children with drug-resistant (DR) TB is likely to be substantial. Because bacterial burden at the site of disease is often low, diagnosis involves collection of multiple specimens and a laboratory capable of performing culture, although the Xpert MTB/RIF assay has improved sensitivity over smear examination. The basic principles of treatment for children are the same as those for adults with MDR-TB; however, the treatment regimen is often empiric and based on the drug susceptibility pattern of the source case, if available, or on past history of treatment. Additional challenges arise when MDR-TB is diagnosed and managed in the context of HIV coinfection. HIV-infected children are also treated with antiretroviral therapy medications, which have the potential to interact with second-line anti-TB drugs. Lack of pediatric formulations of second-line drugs and paucity of pharmacokinetic data make dosage challenging. However, when treated appropriately, children with DR TB have good outcomes.