Summary: The process of dendritic cell differentiation is governed by a tightly controlled signaling network regulated by cytokines and direct interaction between progenitor cells and bone marrow stroma. Notch signaling represents one of the major pathways activated during direct interaction between hematopoietic progenitor cells and bone marrow stroma. Wnt pathway is activated by soluble proteins produced by bone marrow stroma. Until recently, the role of Notch and Wnt signaling in the development of myeloid cells and dendritic cells in particular remained unclear. In this review, we discuss recent exciting findings that shed light on the critical role of Notch and Wnt pathways, their interaction in differentiation and function of dendritic cells, and their impact on immune responses.