Leishmaniasis, a disease caused by *Leishmania* parasites transmitted by sandflies, affects millions of people worldwide. The disease has two main forms: visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL), with additional manifestations such as mucocutaneous leishmaniasis (MCL), diffuse cutaneous leishmaniasis (DCL), recidivans leishmaniasis (LR), and post-kala-azar dermal leishmaniasis. The global burden of leishmaniasis remains stable, but increasing HIV coinfections, migration, and resettlement pose new challenges. Recent advancements in chemotherapy include new drugs and formulations, such as AmBisome, miltefosine, paromomycin, and sitamagaine, which have shown promise in treating VL and CL. However, the misuse and overuse of standard pentavalent antimonials (Sb(V)) for VL treatment have led to widespread resistance, particularly in North Bihar, India. The mechanisms of drug resistance in *Leishmania* species are complex and involve changes in drug metabolism, target site affinity, and efflux pumps. The article discusses the factors affecting drug efficacy, including host immune status, pharmacokinetics, and species variation, and highlights the need for monitoring and surveillance to prevent the spread of resistance.Leishmaniasis, a disease caused by *Leishmania* parasites transmitted by sandflies, affects millions of people worldwide. The disease has two main forms: visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL), with additional manifestations such as mucocutaneous leishmaniasis (MCL), diffuse cutaneous leishmaniasis (DCL), recidivans leishmaniasis (LR), and post-kala-azar dermal leishmaniasis. The global burden of leishmaniasis remains stable, but increasing HIV coinfections, migration, and resettlement pose new challenges. Recent advancements in chemotherapy include new drugs and formulations, such as AmBisome, miltefosine, paromomycin, and sitamagaine, which have shown promise in treating VL and CL. However, the misuse and overuse of standard pentavalent antimonials (Sb(V)) for VL treatment have led to widespread resistance, particularly in North Bihar, India. The mechanisms of drug resistance in *Leishmania* species are complex and involve changes in drug metabolism, target site affinity, and efflux pumps. The article discusses the factors affecting drug efficacy, including host immune status, pharmacokinetics, and species variation, and highlights the need for monitoring and surveillance to prevent the spread of resistance.