The global fight against tuberculosis faces its greatest challenge in drug-resistant strains, where traditional antibiotics fail and patients endure grueling multi-year treatment regimens. Understanding who succeeds versus fails in these intensive protocols could reshape how clinicians approach care for the world's deadliest infectious disease. Lithuanian researchers analyzed treatment outcomes for 5,761 adults with drug-resistant pulmonary tuberculosis across 22 years, revealing dramatic improvements in success rates from 66% to nearly 80% between 2000-2021, while mortality dropped from 31% to below 30%. The study identified specific patient characteristics that predict treatment failure, including active smoking, alcohol dependency, substance abuse, and certain comorbidities that compromise immune function during the lengthy therapeutic process. This represents one of the largest long-term cohort studies examining drug-resistant TB outcomes in a high-burden European setting. The findings carry particular weight because Lithuania historically reported among Europe's highest rates of multidrug-resistant tuberculosis, making it a critical laboratory for understanding treatment dynamics. While the improved success rates suggest better drug regimens and clinical protocols have emerged over two decades, the persistent mortality rates underscore that drug-resistant TB remains formidable. The identification of modifiable risk factors like smoking and alcohol use opens pathways for targeted interventions that could boost treatment success beyond pharmaceutical improvements alone. For clinicians managing these complex cases, the research provides evidence-based guidance for stratifying patient risk and potentially intensifying supportive care for those most vulnerable to treatment failure.