Innate recognition of infection in vertebrates can lead to the induction of adaptive immune responses through activation of dendritic cells (DCs). DCs are activated directly by conserved pathogen molecules and indirectly by inflammatory mediators produced by other cell types that recognise such molecules. In addition, it is likely that DCs are activated by poorly characterised cellular stress molecules and by disturbances in the internal milieu. The multiplicity of innate pathways for DC activation may have evolved to ensure that any signs of infection are detected early, before overwhelming pathogen replication. Understanding which of these signs are both necessary and sufficient to convert DCs into the immunostimulatory antigen-presenting cells that prime appropriate effector T cells may hold the key to improved strategies for vaccination and immunotherapy.