The migration of dendritic cells (DCs) to lymph nodes (LNs) is pivotal to the establishment of the immune response. DCs have been proved to pass through the afferent lymphatic pathway to enter LNs from the peripheral tissues after they have scanned for self or nonself antigens. In response to danger signals, both myeloid and plasmacytoid DC precursors (mDC and pDC precursors) are rapidly mobilized into the circulation. mDC precursors are recruited to inflamed tissues in response to inflammatory chemokines and then remobilized to regional LNs in response to CCL21. In contrast, pDC precursors directly transmigrate to regional LNs via high endothelial venules in a CXCL9- and E-selectin-dependent manner. Such migration is largely dependent on systemic inflammatory reactions. After accumulating in the LNs through distinct trafficking pathways, DCs interact with lymphocytes temporally and spatially to establish effective immune responses. The inflammation-dependent, chemokine-driven property of DC precursor trafficking is a very sophisticated host defense system.