After decades of decline, tuberculosis (TB) cases are continuously increasing worldwide, mostly in developing countries. Although it has not been regarded as fatal now, the TB situation may become worse with the appearance of multi-drug resistant strains (MDR-TB) that do not respond to the most common anti-TB medications, isoniazid and rifampicin. In certain cases, even more severe drug-resistant TB may emerge. Extensively drug-resistant (XDR-TB), is a form of multidrug-resistant TB that also exhibits resistance to other anti-TB agents. The enoyl acyl carrier protein reductase (InhA) enzyme, a crucial regulator of TB mycolic acid biosynthesis, is attracting considerable attention as a druggable molecular target for combating TB and surmounting its resistance mechanisms. The current review covers the currently available anti-TB medications, including the most recently FDA-approved therapy, highlighting their modes of action. In addition, it provides brief structure-activity relationship data and resistance mechanisms halting their efficacy, with a special focus on InhA as an emerging anti-TB target, as well as an overview of the most promising novel lead inhibitors classified according to their chemical entities.