Available data show that Africa, together with the Americas and western and central Europe, reported the lowest prevalence of multidrug-resistant tuberculosis (MDR-TB). However, sub-Saharan Africa has a high TB incidence and the highest human immunodeficiency virus (HIV) prevalence in the world, and because of the high number of TB cases, Africa still presents 14% of the global burden of new MDR-TB cases. Until recently, Africa and South America were deprived of second-line antituberculosis drugs, preventing the development of extensively drug-resistant TB (XDR-TB). Current efforts, introducing improved laboratory infrastructure and second-line TB treatment in resource-limited countries, need to be carried out with care to minimize the development of MDR/XDR-TB in these countries. Recent diagnostic developments now need evaluation and implementation in resource-limited areas, and delays in diagnosis also need to be addressed. Outcomes for MDR/XDR-TB have improved, but prevention of MDR/XDR-TB by early diagnosis and treatment, improvement of adherence, and proper infection control remains the mainstay for the future.