Exposure to a person with infectious TB can result in one of three outcomes: the innate immune system can clear the infection immediately, leaving no evidence of exposure to TB; Mycobacterium tuberculosis organisms can begin to proliferate immediately, causing so-called primary TB; or the growth of organisms can be controlled or contained but not stopped by the host patient's immune response, setting up a state of latent infection. In this state, viable organisms are contained intracellularly within macrophages and within granulomas. 1 People with latent TB are at risk for active TB disease. Lifetime risk of active TB in patients with latent infection, as detected by means of a tuberculin skin test (TST), is estimated to be in the 5% to 10% range, with roughly one-half of that risk occurring in the fi rst year or two after latent infection develops. In addition, the risk of development of reactivation is greater in people with medical conditions associated with immunosuppression, such as infection with HIV or treatment with drugs such as corticosteroids or tumor necrosis factor antagonists. 2 In the United States, treatment of latent infection is a key component of the overall public health plan for controlling TB. 3 Cases of active TB in the United States have fallen steadily since 1992, and the overall rate of TB in this country now stands at 4.3/100,000, the lowest prevalence that has been recorded here. 4 The sharp decline in TB in the United States over the last several years has largely come about because of efforts aimed at diagnosing and treating patients with active disease, thereby reducing transmission and secondary cases. However, if TB is to be eliminated in this country (a stated goal of the US Public Health Service), there is no question that efforts in treating latent TB must be strengthened. 5 A recent study estimates that there is a reservoir of at least 20 million people in this country with latent TB infection, and without treatment, a large number of them will progress to active disease. 6 Furthermore, the majority of cases of active TB in this country now occur in people born outside the United States, and treating latent infection in recent immigrants from high-prevalence countries is the only way to prevent cases of active disease from developing.For the past several years, the US Centers for Disease Control and Prevention (CDC) has emphasized After more than a century of relying on skin testing for the diagnosis of latent TB infection, clinicians now have access to blood-based diagnostics in the form of interferon g release assays (IGRAs). These tests are generally associated with higher sensitivity and specifi city for diagnosis of latent TB infection. This article reviews the indications for testing and treatment of latent TB infection in the overall context of a TB control program and describes how IGRAs might be used in specifi c clinical settings and populations, including people having close contact with an active case of TB, the foreign born, and health-care workers.CHEST 2010; 13...