**1. Introduction**

Leishmaniasis is a parasitic disease that occurs in the tropic and subtropics regions, and the parts of southern Europe. The disease is classified among neglected tropical diseases (NTDs) [1]. Leishmaniasis is spread by the bite of phlebotomine sand flies that causes the infection with *Leishmania* parasites. There are three main forms of the disease—cutaneous leishmaniasis (CL) known as the most common form, that causes skin sores; visceral leishmaniasis (VL; kala-azar) is the most severe form, that affects several internal organs; and mucocutaneous leishmaniasis (MCL) that has a chronic and metastatic behavior [2, 3].

Although the disease has been known for more than 120 years, the number of drugs used for the treatment is still limited to 5–6. The first-line drugs used against leishmaniasis are pentavalent antimony (SbV) compounds namely sodium stibogluconate (Pentostam®) and meglumine antimonate (Glucantime®), which was introduced into treatment more than 70 years ago, despite all their side effects. Neither their mechanism of action nor their chemical structures have been clarified/verified yet in spite of their wide use for a long time. Other drugs used in *Leishmania* infections are liposomal amphotericin B (L-AmB), miltefosine, paromomycin (aminosidine), and azole-derived antifungals; ketoconazole, itraconazole, and fluconazole.

The need for effective, safe, and selective chemotherapeutics against leishmaniasis increases every day. Targeting distinct molecular pathways is a widely used strategy in rational drug design and discovery for developing such agents to treat leishmaniasis. In this chapter, we would like to focus on enzymes which being targeted by the researcher for antileishmanial studies.
