As the most versatile antigen-presenting cells (APCs), dendritic cells (DCs) function as the cardinal commanders in orchestrating innate and adaptive immunity for either eliciting protective immune responses against canceration and microbial invasion or maintaining immune homeostasis/tolerance. In fact, in physiological or pathological conditions, the diversified migratory patterns and exquisite chemotaxis of DCs, prominently manipulate their biological activities in both secondary lymphoid organs (SLOs) as well as homeostatic/inflammatory peripheral tissues in vivo. Thus, the inherent mechanisms or regulation strategies to modulate the directional migration of DCs even could be regarded as the crucial cartographers of the immune system. Herein, we systemically reviewed the existing mechanistic understandings and regulation measures of trafficking both endogenous DC subtypes and reinfused DCs vaccines towards either SLOs or inflammatory foci (including neoplastic lesions, infections, acute/chronic tissue inflammations, autoimmune diseases and graft sites). Furthermore, we briefly introduced the DCs-participated prophylactic and therapeutic clinical application against disparate diseases, and also provided insights into the future clinical immunotherapies development as well as the vaccines design associated with modulating DCs mobilization modes.