Drug-resistant tuberculosis (DR-TB) represents a major programmatic challenge at the national and global levels. Only ∼30% of patients with multidrug-resistant TB (MDR-TB) were diagnosed, and ∼25% were initiated on treatment for MDR-TB in 2016. Increasing evidence now points towards primary transmission of DR-TB, rather than inadequate treatment, as the main driver of the DR-TB epidemic. The cornerstone of DR-TB transmission prevention should be earlier diagnosis and prompt initiation of effective treatment for all patients with DR-TB. Despite the extensive scale-up of Xpert® MTB/RIF testing, major implementation barriers continue to limit its impact. Although there is longstanding evidence in support of the rapid impact of treatment on patient infectiousness, delays in the initiation of effective DR-TB treatment persist, resulting in ongoing transmission. However, it is also imperative to address the burden of latent drug-resistant tuberculous infection because it is estimated that many DR-TB patients will become infectious before seeking care and encounter various diagnostic delays before treatment. Addressing latent DR-TB primarily consists of identifying, treating and following the contacts of patients with MDR-TB, typically through household contact evaluation. Adjunctive measures, such as improved ventilation and use of germicidal ultraviolet technology can further reduce TB transmission in high-risk congregate settings. Although many gaps remain in our biological understanding of TB transmission, implementation barriers to early diagnosis and rapid initiation of effective DR-TB treatment can and must be overcome if we are to impact DR-TB incidence in the short and long term.