It is estimated that 2 million children (younger than 15 years of age) are infected with multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (TB), known as MDR-TB infection.1 Data on the natural history of TB infection—which are often extrapolated to MDR-TB infection—show that young children (younger than 5 years of age) with TB infection are at high risk (up to 25%) of progressing to TB disease within 2–3 years of exposure, with infants’ risk of progression approaching 50%.2 It is noteworthy that older children and adolescents (10–20 years of age) also have an increased risk of developing TB disease after infection. Most children who develop MDR-TB disease are not diagnosed and started on appropriate therapy; mortality is high. However, even if diagnosed and treated, individuals must tolerate long (up to 18–24 months) courses of therapy with multiple (4–6) second-line drugs associated with far more adverse effects (AEs) than the 6–9 months of treatment with first-line drugs for drug-susceptible (DS)-TB disease. Thus, treatment of MDR-TB infection (often referred to as “preventive therapy”) to prevent progression to disease is critical.