Individuals exposed to a person with infectious multidrug-resistant or rifampicin-resistant (MDR-RR) tuberculosis are at risk of developing tuberculosis disease. Historically, insufficient empirical evidence for preventive treatment in this group has permitted inadequate guidance for clinical decision making. However, several high-quality studies have been published detailing preventive treatment options for these contacts at high risk. In this Review, we discuss the management of individuals exposed to patients with infectious MDR-RR tuberculosis. We pay particular attention to the entire spectrum of clinical care for this population, including baseline assessment, possible preventive treatments, follow-up, and shared decision making. We discuss the available evidence, the rationales for different management strategies, and the interactions with (and implications of) secondary comorbidities such as HIV or malnutrition.