Host-directed therapies offer novel opportunities for the fight against tuberculosis

•HDT offers novel opportunities as treatment for TB.•HDT may prove useful to combat MDR and XDR-TB.•Intracellular high-throughput phenotypic assays accelerates drug discovery of HDT.•These advances could lead to the development of new anti-TB drugs. Tuberculosis (TB) remains a leading global health problem that is exacerbated by the emergence of multidrug and extensively drug-resistant Mycobacterium tuberculosis strains. Control of the disease requires novel therapeutic strategies. Modulating host homeostasis appears to be a promising approach, and recent studies have identified novel potential host targets and compounds that could be investigated for host-directed therapies (HDTs). Moreover, the recent development of intracellular high-throughput phenotypic assays makes it possible to screen large libraries of compounds to identify more rapidly new effectors for mycobacterial elimination. Technological advances combined with the novel HDT concept opens an interesting and promising research area that could ultimately deliver personalized TB treatment.