Despite dramatic advances in diagnosis and treatment, tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide. World Health Organization (WHO) reports that one-third of the global population is infected by M. tuberculosis. Direct identification of individuals who are latently infected with live M. tuberculosis without active disease is currently not possible (Latent TB Infection, LTBI). Available immunodiagnostic tests, i.e. Tuberculin Skin Testing and Interferon-gamma Release Assay, ascertain a state of M. tuberculosis specific immune response; they have several limitations in their ability to predict the risk of developing TB disease. Protective efficacy of isoniazid preventive treatment for 6 to 12 months was proved among non-HIV-infected and HIV-infected individuals. The frequency of symptomatic hepatitis due to isoniazid has been estimated to be 1 to 3 per 1,000 persons. The protection of isoniazid treatment in HIV-infected persons appears to be short-lasting (1-2.5 years), in areas with a high incidence of TB. Isoniazid plus rifampicin for 3 months has proven efficacy. There are not sufficient data on preventive treatment for contacts of patients with drug-resistant TB; existing recommendations are based on expert opinions. Rifampicin for 4 months is a choice for the treatment of individuals exposed to an index case with isoniazid-resistant TB. WHO does not recommend anti-TB second-line drugs for preventive therapy.