According to recent data from the Global Burden of Disease Study, there is a positive trend in the burden of disease associated with tuberculosis (TB) in Eastern Europe. Whereas in the 1990s, mortality, incidence and prevalence rates were all increasing, the period from 2000 to 2013 showed improvements in these indicators, with annual declines in all three indicators.1 Nevertheless, an important burden of TB persists in these primarily middle-income countries, and articles in this special supplement highlight the persistence of TB and the high burden of drug-resistant TB in the region, underscoring the need for intensified efforts and innovative thinking in tackling this ancient disease. Efforts over the last two decades, including the introduction of the basic tenets of the DOTS strategy, have improved the treatment of drug-susceptible TB, with high levels of treatment success shown by Lucenko et al. in Latvia,2 and improved treatment success in Moldova with the use of incentives, as shown by Ciobanu et al.3 However, both of these studies highlight the burden of TB among the most vulnerable sectors of the population, such as those with high levels of unemployment, imprisonment and substance use, and suggest that more innovative approaches are required to improve outcomes for these patient groups. A number of articles in this supplement outline the alarming extent of the epidemic of drug-resistant TB in the region. In several countries, multidrug-resistant TB (MDR-TB) is now equally as common as drug-susceptible TB.4,5 While MDR-TB may have emerged initially through a combination of inadequate treatment and poor drug quality, molecular epidemiology data presented by Toit et al. from Estonia suggest that the epidemic is now driven primarily by direct transmission of drug-resistant strains, including extensively drug-resistant TB (XDR-TB).6 These data highlight the point that while it is important to improve the diagnosis and treatment of drug-susceptible TB, this alone will not resolve the MDR-TB epidemic, and there is a need for increased efforts to improve MDR-TB case detection, early diagnosis and effective treatment provision to interrupt transmission. While promising data are shown for Latvia, with potential declines in MDR-TB after a decade of universal diagnosis and second-line treatment,7 other countries, such as Belarus and Ukraine, demonstrate less than ideal case detection and poor treatment outcomes.8,9 In particular, several studies demonstrate high levels of loss to follow-up or failure to complete second-line treatment for MDR-TB,9,10 a challenge that is reported globally,11 with up to 50% of patients failing to complete treatment. Several countries have fallen back on authoritarian approaches whereby all patients are hospitalised for long durations to ensure treatment adherence, sometimes forcibly. While some patients will require hospitalisation for MDR-TB treatment, extensive and/or forced hospitalisation often has negative public health consequences, as patients are understandably reluctant to seek diagnosis and treatment, and may be more likely to default from care. Maintaining infection control in in-patient facilities to a sufficient standard is extremely difficult and costly, with consequent transmission risks for both patients and health care workers.12,13 Even with relatively good infection control measures, superinfection with highly resistant TB strains has been shown to occur.14 In this supplement, Klimuk et al. present data suggesting high levels of TB in health care workers from in-patient TB facilities in Belarus.15 The threat of incarceration is often a deterrent to case detection, and is not conducive to the patient-centred model of care that is required to tackle MDR-TB effectively. Greater recognition that both TB16 and MDR-TB can be treated on an ambulatory basis is needed. Ultimately, however, a better regimen that is more tolerable, shorter and more efficacious will be needed to produce better patient outcomes.17 The articles included in this supplement have arisen from the Structured Operational Research and Training Initiative (SORT IT). This results-driven programme, led by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization (WHO-TDR), was organised by WHO-TDR; the WHO Regional Office for Europe; Medecins Sans Frontieres (Brussels); the International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; and The Union South-East Asia Office, New Delhi, India. As this supplement shows, relatively inexperienced researchers can, with structured support, produce practical, relevant and multidisciplinary operational research that can lead to direct programmatic improvements, with potential broader benefits.