Treatment with biologic agents, in particular tumor necrosis factor alpha (TNF-α) inhibitors, is associated with an increased risk of tuberculosis (TB), and screening and treatment for latent TB infection (LTBI) in patients undergoing such treatment is therefore indicated. The risk of TB associated with different biologics varies significantly, with the highest relative risks, 29.3 and 18.6, associated with adalimumab and infliximab, respectively. The risk of TB with newer TNF-α inhibitors and other biologics appears to be lower. Performance of LTBI screening tests is affected by immune-mediated inflammatory diseases and immunosuppressive therapy in patients due to commence TNF-α inhibitor treatment. Interferon gamma release assays (IGRAs) have a higher specificity than the tuberculin skin test (TST) in patients with Bacillus Calmette-Guérin (BCG) vaccination and have probably a better sensitivity than TST in immunosuppressed patients. LTBI screening programs prior to commencement of anti-TNF-α treatment significantly reduce the incidence of TB, but the optimal screening algorithm, in particular the question of whether a combination of IGRA and TST or a single test only should be used, is a matter of ongoing debate. Use of TST in combination with IGRA is justified to increase sensitivity. Repeat testing for LTBI should be limited to patients at increased risk of TB. If TB develops during anti-TNF-α treatment, it is more likely to be disseminated and extrapulmonary than are other TB cases. Discontinuation of anti-TNF-α treatment in patients diagnosed with TB is associated with an increased risk of immune reconstitution inflammatory syndrome, which is probably best managed by reintroduction of anti-TNF-α treatment.