Management of drug-resistant tuberculosis (TB) is challenging. In areas with high prevalence of drug-resistant TB, we recommend starting all patients with active TB on the standard four or five drug regimens. For patients with acquired drug resistance due to prior inadequate therapy, we advocate thorough evaluation of history and drug susceptibility followed by individualized regimens of at least three drugs. Drugs are most effective if the patient has never received them before and if the patient's tubercle bacilli are susceptible to them in vitro. Retreatment regimens are of long duration and often there are adverse drug reactions. These factors must be put into perspective because options for alternate therapy may be limited. Compliance must be assured.