New diagnostics for tuberculosis are urgently needed to replace or facilitate acid-fast bacilli (AFB) microscopy for the identification of smear-positive cases, and to improve the diagnosis of AFB smear-negative cases. These need to be appropriate for use in low income countries. Tests to replace or facilitate AFB microscopy must offer improvements to this test, including increased sensitivity, speed, ease of use, and safety. Products to improve the identification of smear-negative cases should focus on the diagnosis of patients with paucibacillary pulmonary disease, including children and human immunodeficiency virus (HIV) infected persons, and those with extrapulmonary forms of tuberculosis.