 New classes of antitubercular drugs, diural quinolines and nitroemidazoles, have been associated with improved outcomes in the treatment of drug-resistant tuberculosis, but that success is threatened by emerging drug resistance. We report a case of bedaqueline and delaminated resistance in a 55-year-old woman in South Africa, with extensively drug-resistant tuberculosis and known HIV. This article was authored by James Millard, Stephanie Rimmer, Kemunimo, and others.