Publisher Summary This chapter describes how the dendritic cell system (DCs), distinguished initially in part by its lack of phagocytic activity, can use phagocytosis to present antigens. A critical distinction is to consider the immature stage of the DC life history. It has been known for some time that there are two separate pathways of white cell differentiation that yield macrophages and DCs. Macrophages are specialized for high capacity, continued endocytic activity followed by thorough digestion, while DCs only endocytose for a brief stage of their life history efficiently targeting the internalized substrates for presentation of MHC-peptide complexes. Much of the early literature failed to detect significant accumulation of endocytic substrates by the DCs of the T cell areas in vivo. However, there are three features that need to be taken into consideration. First, DCs restrict their endocytic activity for many substrates to the immature stage of development. Second, certain substrates are internalized much better than others. Third, the best way to detect endocytosis is not to look for the antigen per se, but to look for the major histocompatibility complex-peptide complexes that arise from that antigen. It is suggested that the targeting of phagocytic stimuli to DCs should prove valuable for controlling T cell responses to cellular and microbial antigens. In the steady-state, phagocytosis of apoptotic cells by DCs may lead to tolerance, while in inflammatory states, uptake of microbes and necrotic cells may be pivotal to strong T cell-mediated immunity.