Recognition of molecular signatures of potential pathogens via toll-like receptors (TLRs) activates dendritic cells (DC), leading to the initiation of adaptive immunity. TLR signalling in DC causes an increase in display of MHC peptide ligands for T cell recognition, upregulation of co-stimulatory molecules important for T cell clonal expansion and secretion of immunomodulatory cytokines, which direct T cell differentiation into effectors. Remarkably, ligation of distinct TLRs can trigger differential cytokine production in a single DC type or result in different cytokines in distinct DC sub-types. Studying the complexity of DC responses to TLR ligands illuminates the link between innate recognition and adaptive immunity, paving the way for improved vaccines and strategies to induce tolerance to autoantigens or allografis.