As the incidence of tuberculosis in the United States has increased over the past 10 years, the number of cases caused by drug-resistant organisms has risen dramatically. The genetic mechanisms of resistance, which could lead to better methods of diagnosis and treatment, are being determined. Treatment of drug-resistant tuberculosis is complex, requiring the use of several toxic drugs over 9 to 18 months. At present, drug resistance is fairly localized and can be avoided in most communities if appropriate public health measures are taken. Stronger attention to treatment regimens and adherence with treatment will prevent further emergence of drug-resistant tuberculosis.