Retreatment of tuberculosis involves the management of entities as diverse as relapse, failure, treatment after default, and poor patient adherence to the previous treatment. The emergence of conditions for selection of resistance (failure and partial abandonment) is a matter of great concern. The development of a retreatment regimen for tuberculosis requires consideration of certain basic premises. The importance of a comprehensive and directed history of drugs taken in the past, and the limited reliability of susceptibility tests to many of these drugs, should be kept in mind. Taking this into account, and possessing a thorough knowledge of all anti-tuberculosis medications, it is possible to cure almost all patients with an appropriate retreatment regimen including a minimum of three or four drugs not previously used. Nonetheless, the treatment of these patients is so complex that it should only be carried out by experienced staff. Concern about treating tuberculosis patients with drug resistance varies greatly depending on the available resources. High-income countries should provide individual treatment regimens adapted to each patient; however, in other settings, restricted resources could justify the implementation of standardised therapeutic guidelines with second-line drugs in order to facilitate management and reduce costs.