WHO has developed guidelines on systematic screening for active tuberculosis (TB) based on a thorough review of available evidence. Early detection of TB is essential to further improve health outcomes for people with TB, and to reduce TB transmission more effectively. Systematic screening in high risk groups is a possible complement to efforts to improve the patient-initiated pathway to TB diagnosis (that is, diagnosing TB among people who actively seek care with TB symptoms, also called “passive case-finding”). The available evidence suggest that screening, if done in the right way and targeting the right people, may reduce suffering and death. However the review also highlights several reasons to be cautious. As discussed in detail in this document, there is a need to balance potential benefits against the risks and costs of screening. Some risk groups should always be screened, whereas the prioritization of other risk groups as well as the choice of screening approach depend on the epidemiology, the health-system context, and the resources available. This document sets out basic principles for prioritizing risk groups and choosing a screening approach. It emphasizes the importance of assessing the epidemiological situation, adapting approaches to local situations, integrating TB screening into other health-promotion activities, minimizing the risk of harm to individuals, and engaging in continual monitoring and evaluation.