Toll-like receptor (TLR) signals induce dendritic cell (DC) differentiation and influence the immunological outcome of their interactions with T cells. Recent in vitro studies demonstrate that TLR signals also trigger striking reorganisation of the DC vacuolar compartments, the cytoskeleton and the machinery of protein translation and turnover. Moreover, TLR ligation within endosomes and phagosomes appears to establish organelle autonomous signals. These changes, which mostly occur within minutes to a few hours after TLR engagement, are adaptations relevant to the antigen capture, processing and migratory phases of the DC life history.