Leishmaniasis is a neglected disease caused by protozoan parasites of the Leishmania genus, which affects many people in several countries. This disease has three major clinical forms: cutaneous, mucocutaneous and visceral. The current treatments consist of an intravenous, intralesional or intramuscular administration of pentavalent antimonials, but other drugs can be used, among them, amphotericin B, pentamidine, paromomycin and miltefosine. However, these therapies have many side effects. Hence, there is an increase of studies searching for new formulations using different technologies and different routes of administration for leishmaniasis treatment. Paromomycin sulfate (PM) is an aminoglycoside antibiotic, belonging to class III of biopharmaceutical classification system, used intravenously and topically with leishmanicidal activity. This review will provide a general overview of PM current leishmaniasis treatments and new PM formulations. Treatments using PM are available in ointments or creams for topical administration and PM solution for intramuscular administration. The topical treatment with PM presents low efficacy, probably related to low drug permeability across the skin. To improve PM permeability and efficacy, researchers are establishing micro and nanotechnologies. However, further studies are still required to investigate more physicochemical properties and in vitro/in vivo parameters.