The study of murine dendritic cell (DC) development has been integral to the identification of specialized DC subsets that have unique requirements for their form and function. Advances in the field have also provided a framework for the identification of human DC counterparts, which appear to have conserved mechanisms of development and function. Multiple transcription factors are expressed in unique combinations that direct the development of classical DCs (cDCs), which include two major subsets known as cDC1s and cDC2s, and plasmacytoid DCs (pDCs). pDCs are potent producers of type I interferons and thus these cells are implicated in immune responses that depend on this cytokine. Mouse models deficient in the cDC1 lineage have revealed their importance in directing immune responses to intracellular bacteria, viruses, and cancer through the cross-presentation of cell-associated antigen. Models of transcription factor deficiency have been used to identify subsets of cDC2 that are required for T helper (Th)2 and Th17 responses to certain pathogens; however, no single factor is known to be absolutely required for the development of the complete cDC2 lineage. In this review, we will discuss the current state of knowledge of mouse and human DC development and function and highlight areas in the field that remain unresolved.