is the causative agent of infantile visceral leishmaniasis (VL) in the Mediterranean region. Despite developing protective responses, the disease progresses due to many of factors. These include the action of suppressive cytokines, exhaustion of specific T cells, loss of lymphoid tissue, and defective humoral response. Genetic changes that occur inside the genome of alienated or parasite cells, along with immune responses, play an important role in controlling or progressing the disease. Proapoptotic proteins such as Smac/DIABLO, EndoG, AIF (apoptosis-inducing factor), and cytochrome C are effective in apoptosis. EndoG is a mitochondrion-specific nuclease that translocates to the nucleus during apoptosis. Once released from mitochondria, endoG cleaves chromatin DNA into nucleosomal fragments independently of caspases. Therefore, endoG represents a caspase-independent apoptotic pathway initiated from the mitochondria. A comprehensive understanding of the immune and genetic events that occur during VL is very important for designing immunotherapy strategies and developing effective vaccines for disease prevention. In this review which explained the immunological responses and also the important factors that can contribute to parasite apoptosis and are used in subsequent studies as a target for the preparation of drugs or recombinant vaccines against parasites are briefly reviewed.