Tests that detect Mycobacterium tuberculosis antigens in clinical specimens could provide rapid direct evidence of active disease. We performed a systematic review to assess the diagnostic accuracy of antigen detection tests for active tuberculosis (TB) according to standard methods and summarized test performance using bivariate random effects meta-analysis. Overall, study quality was a concern. For pulmonary TB (47 studies, 5,036 participants), sensitivity estimates ranged from 2% to 100% and specificity from 33% to 100%. Lipoarabinomannan (LAM) was the antigen most frequently targeted (23 studies, 49%). The pooled sensitivity of urine LAM was higher in HIV-infected than HIV-uninfected individuals (47%; 95% confidence interval [CI], 26 to 68% versus 14%; 95% CI, 4 to 38%); pooled specificity estimates were similar: 96%; 95% CI, 81 to 100% and 97%; 95% CI, 86 to 100%, respectively. For extrapulmonary TB (21 studies, 1,616 participants), sensitivity estimates ranged from 0% to 100% and specificity estimates from 62% to 100%. Five studies targeting LAM, ESAT-6, Ag85 complex, and the 65-kDa antigen in cerebrospinal fluid, when pooled, yielded the highest sensitivity (87%; 95% CI, 61 to 98%), but low specificity (84%; 95% CI, 60 to 95%). Because of the limited number of studies targeting any specific antigen other than LAM, we could not draw firm conclusions about the overall clinical usefulness of these tests. Further studies are warranted to determine the value of LAM detection for TB meningitis in high-HIV-prevalence settings. Considering that antigen detection tests could be translated into rapid point-of-care tests, research to improve their performance is urgently needed.The World Health Organization (WHO) estimates that in 2009, 9.4 million new cases of tuberculosis (TB) occurred and 1.7 million people died of the disease (89). The vast majority of these patients live in low-and middle-income countries (LMIC) where TB diagnosis depends primarily on smear microscopy. Microscopy has low sensitivity and does not detect smear-negative TB (77), which may account for 24% to 61% of all pulmonary cases in HIV-infected individuals (27). Improved diagnostic tests, such as mycobacterial culture and nucleic acid amplification (NAA) tests, are available in highincome countries but are often too expensive and complex for routine use by TB control programs in resource-constrained settings in which TB is endemic. Lack of access to diagnostic services in resource-limited settings presents an additional barrier to using these tests. The Xpert MTB/RIF (Cepheid, Inc., Sunnyvale, CA), recently endorsed by the WHO, is rapid and highly sensitive for detection of TB and drug resistance; however, this new technology is costly, preventing its use in many areas where the epidemic is most severe (10). Accurate, rapid, inexpensive, and simple diagnostic tests are urgently needed for TB care and control.There have been considerable efforts over the past 50 years to devise a rapid TB test based on antibody detection. However, substantial ...