First-line drugs for tuberculosis treatment include isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide. Molecular mechanisms for resistance to each of these drugs have been elucidated. In every case, resistance is conferred by mutations in existing genes, not by the acquisition of new genetic material. Drug resistance is a major problem worldwide, but the rates vary widely among countries and within countries. Acquired resistance in previously-treated patients is much more common than primary resistance in patients with no previous treatment. High rates of acquired resistance have been reported from referral centers in Saudi Arabia and Lebanon. Successful TB treatment requires prolonged therapy with at least two active drugs. Directly-observed therapy (DOT) improves success rates and reduces the risk of acquired resistance. TB due to susceptible strains can be cured in over 95% of cases.