Multidrug-resistant tuberculosis (MDR-TB) is a growing global public health threat. MDR-TB affects more than a half-million people worldwide and is characterized by significant morbidity and mortality. New rapid diagnostic methods like GeneXpert and availability of new MDR-TB drugs and shorter treatment regimens hold promise of more patients diagnosed and put on treatment. Major challenges of lack of adequate resources, poverty, and limited access to health care continue to hamper efforts. This article reviews epidemiology, clinical features, management, and treatment, with new updates and recent changes in guidelines that offer patients better tolerated and shorter regimens for enabling therapeutic outcomes.