Antitubercular chemotherapy is the mainstay in the management of spinal tuberculosis. A thorough knowledge about the pharmacokinetics and pharmacodynamics of the first-line drugs is essential for the successful management of the disease. Patients with drug resistance benefit from treatment with second-line drugs. Treatment in spinal tuberculosis is guided by the clinical response to treatment. The author’s preferred regime is 2HRZE/4HR for all fresh cases of spinal tuberculosis who have not received any antituberculous treatment in the past. In case of delayed response do not add a single drug to the regime. Try to get specimen for culture and sensitivity and follow as per culture report. If no specimen is available, follow WHO criteria for such patients.