Leishmaniasis, the most neglected tropical disease caused by protozoan parasites of the genus , poses a substantial global health concern. The present review provides an in-depth overview of current findings on apoptosis and cell death mechanisms in leishmaniasis, integrating current advancements and key components. It explores the intricate interaction between spp. and host cell apoptosis, a crucial basis of disease outcome. spp. and host cell death pathways interplay is highly complex and multi-layered, and the current review discusses how parasites manipulate host cell apoptotic signal transduction to establish and sustain infection. This includes the subversion of intrinsic and extrinsic apoptotic signaling, the modulation of pro- and anti-apoptotic proteins, and managing host cell death machinery for their survival and pathogenesis. Moreover, the present review explores the emerging evidence of apoptosis in parasites. This fascinating phenomenon, while less widely studied, recommends immense therapeutic potential in targeting parasite-persistent mechanisms. Finally, we critically analyze the challenges and future directions in this field, emphasizing the need for a deeper understanding of the merits and mediator molecular mechanisms underlying -induced apoptosis and its implications for novel therapeutic strategies against this debilitating disease.