Leishmaniasis is transmitted by sand flies leading to parasite inoculation into skin. In the mammalian host, the parasite primarily resides in skin macrophages (MΦ) and dendritic cells (DC). MΦ are silently invaded by the parasite eliciting a stress response, whereas DC become activated, release IL-12, and prime antigen-specific T cells. Here we review the basics of the immune response against this human pathogen and elucidate the role and function DC and MΦ for establishment of protective immunity against leishmaniasis. We focus on cell type-specific differences in parasite uptake, phagocyte activation and processing of parasite antigens to facilitate an understanding how their respective function may be modulated e.g. under therapeutic considerations.