The era of the modem chemotherapy in the treatment of tuberculosis has started by the discovery of streptomycin in 1943. Soon after the introduction of SM, it became evident that drug-resistance against streptomycin (SM) quickly emerged when used singly, and the combination therapy with para-aminosalicylate (PAS) and isoniazid (INH), both of which were developed a little later, had been the standard regimens for the treatment of tuberculosis. But, long-term therapy, more than a year, sometimes of two or three years, was required to get recovered from tuberculosis by three-drug combination therapy of SM-PAS-INH. Introduction of rifampicin (RFP) in 1966 and re-evaluation of pyrazinamide (PZA) in early 1970's have brought a revolutionary change in the concept of tuberculosis chemotherapy, and very potent six-month regimen, consisting of two-month initial intensive phase (INH-RFP-PZA and EB or SM) and four-month maintenance phase (INH-RFP) has been established as the global standard regimen. Tuberculosis chemotherapy has liberated tuberculosis patients from lengthy stay in sanatoria or hospitals. Now, tuberculosis patients could be and should be treated by the intensive short-course chemotherapy under ambulatory settings. One of the most serious obstacles of ambulatory treatment is the incompliance of the patients to the prescribed regimen. Obvious outcome of such incompliance is the treatment failure at the level of individual patients and also the prevalence of multidrug-resistant- (MDR-) and extensively drug-resistant- (XDR-) tuberculosis all over the world. MDR-and XDR-tuberculosis are already threatening tuberculosis control policy in some countries and districts in the world. Early diagnosis of infectious patients and successful treatment of newly diagnosed patients under DOTS are the most recommendable strategies to prevent the emergency of MDR-and XDR-tuberculosis worldwide. In Japan, the policy of tuberculosis treatment has been more or less diverged from the global standards, namely, higher rate of hospitalization, longer hospitalization periods, and longer treatment. One of the most important reasons for such cost-effectively inefficient practices is the lack of reliable and practical DOT system for ambulatory treatment. Recently, we successfully completed a trial to implement a DOT system in which the city-pharmacists served as the observer. We believe that this system is well acceptable for both city-pharmacies and tuberculosis patients, and expect to be adapted through the whole country. New anti-tuberculosis drugs which enable the intermittent therapy of much shorter duration are eagerly expected.