Treatment regimens containing multiple drugs are key to overcoming drug resistance and achieving high cure rates. The current standard treatment for drug-susceptible TB is a 6-month regimen containing 4 first-line drugs: isoniazid, rifampin, pyrazinamide and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months. This regimen cures over 95% of patients if compliance is high. However, due to the length of treatment and side effects of drugs, ensuring patient compliance and completion of therapy can be challenging. Higher doses or novel formulations of existing drugs may improve treatment outcomes. For example, increasing the dose of rifampin, a key bactericidal drug, has been shown to improve cure rates and potentially shorten treatment duration in mice. Increased doses of rifampin achieve higher drug exposures and better killing of M. tuberculosis. Similarly, new fixed-dose combination formulations or nanoformulations of existing drugs may help reduce side effects, improve compliance and enhance drug delivery into infected macrophages. New drugs, such as bedaquiline and pretomanid, have significantly improved treatment of drug-resistant TB. When added to standard MDR-TB regimens, bedaquiline increased cure rates from 25% to 71.9% for patients with extensively drug-resistant TB. Pretomanid has been shown to reduce treatment duration to 6-9 months when used in combination with bedaquiline and linezolid. However, emerging resistance to these new drugs is a concern and close monitoring is needed. Reducing treatment duration is key to improving adherence and access to care. Biomarkers and surrogate endpoints that correlate with treatment response, such as changes in M. tuberculosis- specific T cell activation or frequency, may help determine optimal treatment duration for individual patients. Host-directed therapies aimed at enhancing the immune response may also shorten the time to cure. Overall, continued development of new and repurposed drugs, optimized and higher-dose formulations of existing drugs, new combination regimens, and biomarkers to determine optimal treatment duration are critically needed to improve TB treatment outcomes, especially for drug-resistant disease. Shorter, safer, and more effective treatments will be key to achieving TB elimination.