The innate immune system provides many ways to quickly resist infection. The twobest-studieddefenses indendritic cells (DCs) are the productionof protective cytokines—like interleukin (IL)-12 and type I interferons—and the activation and expansion of innate lymphocytes. IL-12 and type I interferons influence distinct steps in the adaptive immune response of lymphocytes, including the polarization of Thelper type 1 (Th1)CD4⁺ T cells, thedevelopment of cytolytic T cells andmemory, and the antibody response. DCs havemany other innate features that do not by themselves provide innate resistance but are critical for the induction of adaptive immunity. We have emphasized three intricate and innate properties of DCs that account for their sentinel and sensor roles in the immune system: (1) special mechanisms for antigen capture and processing, (2) the capacity tomigrate to defined sites in lymphoid organs, especially the T cell areas, to initiate immunity, and (3) their rapid differentiation or maturation in response to a variety of stimuli ranging from Toll-like receptor (TLR) ligands to many other nonmicrobial factors such as cytokines, innate lymphocytes, and immune complexes. The combination of innate defenses and innate physiological properties allows DCs to serve as amajor link between innate and adaptive immunity. DCs and their subsets contribute to many subjects that are ripe for study including memory, B cell responses, mucosal immunity, tolerance, and vaccine design. DC biology should continue to be helpful in understanding pathogenesis and protection in the setting of prevalent clinical problems.