Dendritic cells (DCs) are bone marrow-derived cells that bridge the innate and adaptive immune systems. They are classified into three major subsets: plasmacytoid DCs (pDCs), myeloid/conventional DC1 (cDC1), and myeloid/conventional DC2 (cDC2). Each subset develops under the control of specific transcription factors, with differential levels of IRF8 and IRF4, in collaboration with PU.1, ID2, E2-2, ZEB2, KLF4, IKZF1, and BATF3. DC hematopoiesis is conserved across mammalian species and distinct from monocyte development. Monocytes can differentiate into DCs, especially during inflammation, but quiescent tissues contain significant resident populations of DC lineage cells. Advances in phenotype and gene expression analysis have identified pre-DCs in human blood and heterogeneity among cDC2s, facilitating the integration of mouse and human immunology and supporting efforts to understand human DC function in vivo. Recent studies have also revealed new models of hematopoiesis and the origin of human DCs, highlighting the importance of intrinsic regulatory circuits in defining lineage and the limitations of phenotyping in identifying discrete potentials.Dendritic cells (DCs) are bone marrow-derived cells that bridge the innate and adaptive immune systems. They are classified into three major subsets: plasmacytoid DCs (pDCs), myeloid/conventional DC1 (cDC1), and myeloid/conventional DC2 (cDC2). Each subset develops under the control of specific transcription factors, with differential levels of IRF8 and IRF4, in collaboration with PU.1, ID2, E2-2, ZEB2, KLF4, IKZF1, and BATF3. DC hematopoiesis is conserved across mammalian species and distinct from monocyte development. Monocytes can differentiate into DCs, especially during inflammation, but quiescent tissues contain significant resident populations of DC lineage cells. Advances in phenotype and gene expression analysis have identified pre-DCs in human blood and heterogeneity among cDC2s, facilitating the integration of mouse and human immunology and supporting efforts to understand human DC function in vivo. Recent studies have also revealed new models of hematopoiesis and the origin of human DCs, highlighting the importance of intrinsic regulatory circuits in defining lineage and the limitations of phenotyping in identifying discrete potentials.