Plasmacytoid dendritic cells (PDCs) represent a subset of circulating leukocytes characterized by the ability to release high levels of type I interferon (IFN). Under homeostatic conditions PDCs are confined to primary and secondary lymphoid organs. This is consistent with the restricted profile of functional chemotactic receptors expressed by circulating PDCs (i.e. CXCR4 and ChemR23). Accumulation of PDCs in non-lymphoid tissue is, however, observed in certain autoimmune diseases, allergic reactions and tumors. Indeed, PDCs are now considered to be involved in the pathogenesis of diseases characterized by a type I IFN-signature and are considered as a promising target for new intervention strategies. Here, current knowledge of the molecular mechanisms involved in the recruitment of PDCs under homeostatic and pathological conditions are summarized.