Miltefosine, originally developed as an antitumor agent, has emerged as the first and only FDA-approved oral medication for treating visceral, cutaneous, and mucocutaneous leishmaniasis. With a unique pharmacokinetic profile characterized by slow absorption and a long terminal half-life of approximately 31 days, miltefosine accumulates during treatment to achieve steady-state concentrations. Clinical studies have demonstrated high cure rates (94–97%) in visceral leishmaniasis with standard dosing, and its efficacy extends to various forms of cutaneous leishmaniasis, though with varying response rates depending on the causative species. The drug has shown promise in combination therapy, particularly with liposomal amphotericin B and paromomycin, offering advantages such as reduced treatment duration and decreased risk of drug resistance. While generally well-tolerated, gastrointestinal side effects constitute its major drawback, and its use is contraindicated during pregnancy. Novel topical formulations are under development that could potentially expand its therapeutic applications in dermatological disorders.