Médecins Sans Frontières (MSF) has been working in Uzbekistan since 1998 in close cooperation with the Ministry of Health to improve the diagnosis and treatment of people with tuberculosis (TB), including drug-resistant forms of the disease. In Karakalpakstan, MSF’s scope of work has grown from a focus on direct observation treatment (starting in 1998) to the implementation of a comprehensive care programme for drug resistant and drug sensitive TB and the implementation of the global clinical trial TB-PRACTECAL. In the comprehensive care component of the project, MSF supports the Ministry of Health in its rollout of protocols reflecting global best practices, introduces healthcare innovations through operational research and pilots, and promotes shorter course TB treatment regimens with the use of new and repurposed anti-TB drugs. The TB-PRACTECAL clinical trial is the first ever multi-country, randomized, controlled clinical trial aimed to demonstrate the safety and efficacy of a six-month, all oral regimen for drug-resistant TB.