Tuberculosis caused by Mycobacterium tuberculosis, is still one of the major global health problems. The conventional diagnostic tests for tuberculosis are not sensitive enough and time consuming. Seroimmunologic diagnostic test is one of the early diagnostic technologies in the tuberculosis control and prevention, so much attention has been focused on the development of novel immunological assays of tuberculosis recently. Potential value of Mycobacterium tuberculosis RD region-encoded proteins have been evaluated for rapid diagnosis of tuberculosis these years. In this review, advances in the diagnosis of tuberculosis based on the RD region antigens were discussed.