Tuberculosis (TB) remains a significant public health issue worldwide especially in developing countries, where the disease is endemic, and effective TB diagnostic as well as treatment-monitoring tools are serious barriers to defeating the disease. Detection of pathogen-specific metabolic pathways offers a potential alternative to current methods, which focus on bacterial growth, bacterial nucleic acid amplification, or detection of host immune response to the pathogen. Metabolic pathway detection may provide rapid and effective new tools for TB that can improve TB diagnostics for children and HIV infected patients. Metabolic breath tests are attractive because these are safe, and provide an opportunity for rapid point of care diagnostics and tool for drug efficacy evaluation during clinical trials. Our group has developed a rabbit urease breath test model to evaluate the sensitivity and the specificity of urease based detection of Mycobacterium tuberculosis. TB infected rabbits were given stable isotopically labelled urea as the substrate. The urea tracer was metabolized to 13 C-CO 2 and detected in exhaled breaths using portable infrared spectrometers. The signal correlated with bacterial load both for primary diagnostics and treatment monitoring. Clinical trials are currently ongoing to evaluate the value of the test in clinical management settings. Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and treatment response.