The diagnostic gap remains greater for TB than for any other infectious disease; more than 80% of patients with multi-drug resistance remain undiagnosed or unreported. Many years of lab strengthening efforts have shown that scaling up BSL3 capacity for culture drug susceptibility testing will not be a feasible, or sustainable solution. Remarkable progress has been made in the development and introduction of rapid molecular TB drug susceptibility tests, but limitations notably with regard to ease of use and available drug spectrum hamper the impact on case management. To address drug resistant TB, complimentary diagnostic strategies are necessary: Expanded decentralized drug susceptibility testing to inform regimen choice is required at the point of first patient contact, i.e. at low levels of the health care system, especially given the anticipated introduction of short-course regimens and decentralization of MDR treatment. Comprehensive, rapid DST for individualized therapy must be available at more centralized levels. Where are we on the R&D path to much needed new tools? The understanding of the genetics and clinical mutation relevance of TB drug resistance particularly for second-line drugs and newly developed drugs is rapidly improving. WHO and FIND hosted a meeting earlier this year that essentially concluded that genotypic testing should replace culture DST, but at this stage there is no diagnostic solution available or in development that would allow to actually do this. FIND is working with Rutgers University and Cepheid on an expanded DST cartridge for the Omni platform. Initial performance of the assay is excellent, with >95% sensitivity and >99% specificity for detection of mutations in katG, inhA, gyrA, and rrs, and >81% sensitivity for eis mutations. Other companies also join in and strive to develop expanded molecular DST. Experts agree that next generation sequencing represents the future of TB drug resistance testing, initially for surveillance, but within 5 years for individual patient management, and offers huge potential in terms of speed, comprehensiveness and ease of use. A standardized, all-in one solution would ease deployment. The successful uptake of all novel TB diagnostics will critically depend on a strengthening of the patient care cascade and innovative delivery and testing strategies.