The recent years have witnessed significant progress in the development of new drug candidates for the treatment of TB. While many of these are now in clinical trials, continued research is needed in order to sustain the drug discovery pipeline and meet the increasing needs of TB patients. These include shortening treatment, killing drug-resistant strains, and finding medications compatible with antiretroviral and diabetes therapy. Nowadays, TB drug discovery benefits from high-throughput screening methods, availability of conditional expression systems, and biophysical and biochemical techniques that enable target-based rational drug design. This article reviews the current state of TB drug development and discusses possible approaches to finding new leads.