With the increased number of new leprosy cases in many regions of the world [1], the search for new tools to improve leprosy control must become a priority. The disease is characterized by the presence of debilitating lesions in the skin and peripheral nerves triggered by Mycobacterium leprae infection. Patients can be divided into two groups: paucibacillary (Pb) and multibacillary (Mb). Pb presents a low bacillary load and an active cellular immune response, while Mb has a high bacillary load with a systemic infection, anti-inflammatory cytokines and humoral immune response. Multidrug therapy (MDT) was implemented by WHO in 1981, and its use dropped the incidence of leprosy worldwide. However, cases of relapse after drug discharge point to therapeutic resistance. Besides, the long treatment period and its side effects favor abandonment. Other complications, like erythema nodosum leprosum (ENL) or reversal reaction episodes before, during, or after MDT can accelerate permanent disabilities. Thus, it is important to invest in the identification of therapeutic targets that enhance MDT efficacy and shorten treatment time or avoid complications.