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The tuberculin skin test, now over a century old, is prone to reader variability, and outcomes are influenced by cross-reactivity with environmental mycobacteria, previous bacillus Calmette-Guerin (BCG) vaccination, and anergy in immunosuppressed individuals. More recently, T-cell-based interferon-γ responses to Mycobacterium tuberculosis - specific antigens have been investigated for their role in diagnosing latent tuberculosis infection.We review the evidence supporting the utility of the interferon-γ assay for the diagnosis of latent tuberculosis infection (LTBI) in low-prevalence countries. We discuss the principle of the test, technical factors related to performance, and its utility in active tuberculosis, in specialised subgroups such as immunocompromised patients, and its applicability in developing countries.Compared with the tuberculin skin test, the antigen-specific interferon-γ assay, when used in a standardised protocol (overnight incubation assay using a combination of two antigens) for the diagnosis of LTBI, has greater specificity in BCG-vaccinated individuals, displays a stronger association with exposure, and is less biased by environmental mycobacteria such as Mycobacterium avium. Prospective studies are required, however, to confirm that treating LTBI, as defined by the interferon-γ assay, will reduce the tuberculosis burden in low-prevalence countries and whether interferon-γ responses are predictive of those who have a high risk of progression to active tuberculosis. Further studies are required to address the utility of the interferon-γ assay in specialised subgroups of patients, in developing countries, and as a marker of disease activity.