Multidrug-resistant tuberculosis (MDR-TB) is threatening control of TB in many parts of the world. As a result of limited treatment options, patients have a poor prognosis and low chances of cure. This situation can be exacerbated by HIV epidemics. In some cases, the risk exists of a real shift from susceptible to resistant strains. Despite its relevance, currently there are more contradictions and confusion surrounding MDR-TB than hard evidence. No randomized controlled trials have been performed and published evidence is limited. Rather than just the selection of expensive drugs, MDR-TB management requires well-structured programmes with a comprehensive approach, which involve the actions of a wide range of participants. Even with current investments in research and development, new drugs and vaccines will take many years to be applied in low and middle income countries. The most successful results will depend on the optimization of existing tools. The majority of the patients, even those with extensive patterns of bacilli resistance, have a possibility of cure if current clinical knowledge and effective logistics are applied. This paper is a critical review of current best practice regarding the diagnosis and treatment of MDR-TB.