Visceral leishmaniasis or Kala-Azar is a neglected tropical disease caused by the unicellular kinetoplastid parasite Leishmania donovani.The treatments available have various shortcomings like toxicity and high cost. The development of resistance in the strains makes thetreatment less effective. Hence, there is a need for new and better treatments. DNA topoisomerases are a group of enzymes presentubiquitously in all organisms from unicellular protozoan parasites to humans. These enzymes control the cell's topological problemscaused by DNA double helix during nucleic acid metabolism. However, the leishmanial topoisomerase (LdTOPILS) is very differentfrom the human topoisomerase in structure, expression, and function. Therefore, LdTOPILS acts as a potent target for newer drugs. Adiverse range of compounds has been developed to date against Leishmanial topoisomerases. This review article describes Leishmaniatopoisomerase enzyme's structural and catalytic activity and Topo-targeted antileishmanial drug development. Therefore, this reviewarticle would be beneficial for researchers to understand the structure-function relationship of topoisomerases with their targetedinhibitors.