Leishmaniasis is a severe disease and results in high mortality rates. Despite this, there are few drugs to treat and with various limitations such as toxicity and resistance, which justifies the search for new drugs. Thus, cysteine protease B (CPB) is a promising target against leishmania due to its immunomodulatory function related to the parasite's virulence and its interaction with the host. Thus, this perspective showed the potential of CPB in drug design and the main insights that can be used in subsequent drug design works. In fact, the aziridine analogs are the most explored against CPB due to the promising results and provide several insights into drug design. Also, it is noteworthy that one of the biggest challenges is target selectivity. Knowledge about substrate binding and other factors, such as the reversibility of inhibitors, is also needed. In addition, exploring target selectivity patterns is critical to developing CP inhibitors for clinical use to combat this threatening agent.