The emergence of multidrug-resistant tuberculosis strains and the coinfection with HIV, together with advances in immunology, have led to renewed interest regarding ways to exploit the immune responses against Mycobacterium tuberculosis therapeutically. Here we review the fundamentals of tuberculosis therapy in view of the epidemiological and clinical challenges, and explore the experience with immune-based therapies for the treatment of active tuberculosis. These immune-based therapies are discussed here with the aim of assessing their potential use as adjuncts to chemotherapy.