The host innate immune system represents the first line of defense against invasive pathogens. During the crucial early stages of infection, the host innate immune system must be able to rapidly detect and respond to foreign pathogens, enabling an efficient and successful adaptative immune response. Leishmania parasites are obligate intracellular eukaryotic pathogens living inside cells of the mononuclear phagocytic system. Recent data has proven distinct roles of various phagocytic cells, such as neutrophils, macrophages and dendritic cells during Leishmania infection. There is growing evidence that Leishmania modifies antigen presentation, apoptosis and immunoregulatory functions on these cells, leading to persistent and chronic infection. At the molecular level, the Toll-like receptors (TLR) family is a major player in the early host-pathogen interaction. The TLRs expressed intracellularly or at the surface of the cells involved in the innate immune response recognize conserved structures on foreign pathogens, such as Leishmania, playing a pivotal role in triggering innate and adaptative immune responses. Nonetheless, the same TLRs can be considered as a potential strategic target used by these organisms for their own advantage. In this review, we discussed the findings on the cellular processes involved in the innate host defense against intracellular pathogens, focusing on the Leishmania infection, from the initial host-parasite interactions involved in the parasite recognition to the mechanisms employed to eliminate the pathogen, presenting new data on the role of TLR2 in visceral leishmaniasis.