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Leishmaniasis is a parasitic disease predominantly seen in tropical and subtropical regions. Different Leishmania species are responsible for different forms of the disease: Viscereal Leishmaniasis, Cutaneous Leishmaniasis and Mucutaneous Leishmaniasis. Cutaneous Leishmaniasis, which is caused, by either L. Tropica or L. major affects around 1.5 million people every year. It is transmitted by the bite of the sandfly, an intermediate host. Rodriguez et. al showed that the bisphosphonates, such as pamidronate inhibit the growth of lesions in mice when administered intraperitoneally. BPs target the Farnesyl Diphosphate synthase (FPPS), an enzyme of the mevalonate pathway in both parasite and humans, . Kinetic studies on LmFPPS showed that the Km for DMAPP is 53 µM. Inhibition cell based studies against intracellular L. donovani amastigotes show that the IC50 values for 1-(2-Hydroxy-2,2-bis-phosphono-ethyl) −3-phenyl-pyridinium (300B) and 1-(2,2-Bis-phosphono-ethyl)-3-butyl-pyridinium (476A) are 4.68 µM and 6.48 µM respectively. Isothermal Calorimetric studies with these inhibitors revealed that the binding is entropically driven. X-ray crystallographic structures of the LmFPPS in complex with 300B, Isopentenyl Pyrophosphate (IPP), and 3 divalent cations and the other in complex with 476A, IPP and 3 divalent cations were determined. Comparison of these structures with those of the human enzyme complexed with zolendronate reveals significant differences in residues at the bottom of the pocket, such as Glu97 and Leu129, that could be used to tailor specificity of the bisphosphonates to the parasitic enzyme.