<b>Aim:</b> To evaluate the potential of three benzohydrazones (<b>1</b>-<b>3</b>), four acylhydrazones derived from isoniazid (INH-acylhydrazones) (<b>4</b>-<b>7</b>) and one hydrazone (<b>8</b>) as antituberculosis agents.<b> Materials & methods:</b> Inhibitory and bactericidal activities were determined for the reference <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) strain and clinical isolates. Cytotoxicity, drug combinations and ethidium bromide accumulation assays were also performed. <b>Results:</b> The tested compounds (<b>1</b>-<b>8</b>) presented excellent antituberculosis activity with surprisingly inhibitory (0.12-250 μg/ml) and bactericidal values, even against multidrug-resistant <i>Mtb</i> clinical isolates. Compounds showed high selectivity index, with values reaching 1833.33, and a limited spectrum of activity. Some of the compounds (<b>2</b> & <b>8</b>) are also great inhibitors of bacillus efflux pumps. <b>Conclusion:</b> Benzohydrazones and INH-acylhydrazones may be considered scaffolds for the development of new anti-<i>Mtb</i> drugs.