**1. Introduction**

*Mycobacterium tuberculosis*, the etiological agent of human tuberculosis (TB), represents a global challenge to human health since it is the main cause of death by an infectious disease worldwide. Estimations by the World Health Organization (WHO) reported that the tubercle bacillus latently infects approximately one fourth of the world's population, and it is responsible for more than one million deaths every year [1]. Additional factors such as immunodeficiencies [2] and diabetes [3] increase the risk of developing active TB.

The currently available anti-TB therapy is composed of four antibiotics (rifampicin, isoniazid, pyrazinamide and ethambutol) that must be administered for at least 6 months to patients affected by drug-sensitive pulmonary TB [4]. However, the increasing number of multi- and extensively drug-resistant TB cases [5] requires the use of second- or even third-line anti-TB medications, which are characterized by frequent severe side-effects that reduce patients' compliance [6].

Feeding the drug discovery pipeline with the identification of novel chemical entities and promoting the development of those candidate drugs that are presently in clinical trials are therefore of outmost importance in order to shorten anti-TB treatment.

In this Special Issue of Applied Sciences dedicated to "Tuberculosis Drug Discovery and Development", we review the most recent achievements in drug and target identification and present an update on the clinical development of two candidate compounds (macozinone and delpazolid). An overview of technical advancements is included, together with a summary of the anti-TB vaccines which are either in the discovery or clinical phases.
