**1. Introduction**

*Mycobacterium tuberculosis*, the etiological agent of human tuberculosis (TB), is thought to latently infect approximately one fourth of the world's population and is responsible for over one million deaths every year [1], thus representing the leading cause of mortality by an infectious disease worldwide. Immunodeficiency caused by HIV [2] and co-morbidities like diabetes [3] constitute additional risk factors for the development of active TB disease.

The current anti-TB therapy consists of a combination of four antibiotics (rifampicin, isoniazid, pyrazinamide and ethambutol) that must be administered for at least 6 months in case of drug-sensitive pulmonary TB infection [4]. However, *M. tuberculosis* displays increased resistance to first-line drugs, which has resulted in multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases [5]. Second-line treatment regimens are therefore employed but require longer duration to be effective and are associated with severe side effects that frequently decrease patient compliance [6].

To address the increasing need for new and potent therapeutic options against TB, alternative approaches are being explored. These include host-directed therapy (HDT) and anti-virulence compounds. Within the first choice, a number of molecules that reduce inflammation, modulate autophagy and potentiate the immune response are currently in preclinical and in clinical trials. On the other hand, drugs that affect *M. tuberculosis* ability to infect and kill host cells represent a promising complement to standard antibiotic treatment.

Here we review the current state of research in the areas of HDT and anti-virulence drugs as complementary approaches to TB therapy.
