The post-2015 World Health Organization global tuberculosis strategy recognizes that elimination requires a focus on reducing the pool of latently infected individuals, an estimated 30% of the global population, from which future tuberculosis cases would be generated. Tackling latent tuberculosis infection requires the identification and treatment of asymptomatic individuals to reduce the risk of progression to active disease. Diagnosis of latent tuberculosis infection is based on the detection of an immune response to Mycobacterium tuberculosis antigens using either the tuberculin skin test or interferon-γ release assays. Current treatment requires the use of antibiotics for at least 3 months. In this article, we review the current knowledge of the natural history, immunology, and pathogenesis of latent tuberculosis, describe key population groups for screening and risk assessment, discuss clinical management in terms of diagnosis and preventative treatment, and identify areas for future research.