Dendritic cells (DC) are professional phagocytes possessing a unique ability to sense perturbations in the tissue microenvironment and promote adaptive immune responses, whilst maintaining immunological tolerance. Mouse myeloid DC progenitors with the ability to migrate through the blood and replenish the DC pool have been identified in bone marrow but the ontogeny of human DC is poorly understood. Access to lymphoid tissues for human DC isolation is severely limited and researchers have resorted to the use of in vitro derivation systems in attempts to understand DC development, which may result in misleading conclusions. The identification of a human DC progenitor in blood would greatly enhance the understanding of DC homeostasis and their role in pathogenesis.