Tuberculosis remains one of the top two causes of death caused by a single infectious disease worldwide, despite curative therapy. Children with tuberculosis are especially difficult to detect, since acid fast bacilli smears and cultures are usually negative and clinical signs are nonspecific or lacking. Multidrug-resistant tuberculosis, or tuberculosis resistant to at least isoniazid and rifampin, has emerged in most areas of the world over the past 20 years. Treatment of multidrug-resistant tuberculosis is more expensive and difficult. The second-line tuberculosis medications required for treatment are more toxic and less efficacious than standard treatment. These medications are not readily available in many areas of the world where drug resistance is most common. Fluoroquinolones are one of the most promising classes of second-line medications, but are not generally recommended for use in children. Ethambutol is recommended in the initial treatment of tuberculosis in children treated in areas where there is a risk of drug-resistant disease and the susceptibility of the source case is not known. Some experts have been hesitant to use ethambutol due to the risk of visual impairment associated with the drug and the difficulties in monitoring vision in young children. Pediatric drug formulations are not available for most antituberculosis medications, even the first-line tuberculosis drugs. Treatment of children exposed, infected or ill with multidrug-resistant tuberculosis is reviewed with special emphasis on second-line drugs, including recommended dosage, available formulations and necessary monitoring. While new cases of multidrug-resistant tuberculosis have decreased in most developed countries over the past 10 years, cases continue to increase in many developing countries and among immigrants from high-risk areas. Tuberculosis and multidrug-resistant tuberculosis are serious threats requiring worldwide strategies to control and treat. Better diagnostic tests, medications, public health strategies and vaccines will all be needed to eliminate tuberculosis.