Preventive vaccination is the most successful approach against infectious diseases and has a great impact on world health. Vaccines operate through the activation of innate immunity that helps to stimulate antigen-specific T- and B-lymphocytes. These events are orchestrated by dendritic cells (DCs) that are able to sample foreign structures and concomitantly sense 'danger signals'. Thus, DCs provide a functional link between innate and acquired immunity, and due to their regulatory potential are referred to as natural adjuvants. Human conventional and plasmacytoid DCs express different sets of well-characterized Toll-like membrane receptors (TLRs) that recognize a broad range of conserved molecular patterns of pathogens. The recently discovered cytosolic Nod-like receptors (NLRs) and RIG-like helicases (RLHs) also turned out to participate in pathogen recognition and modulation of immune responses through interacting signaling pathways. As a result of their collaboration, the TLR, NLR and RLH recognition systems induce the secretion of different combinations of cytokines that play a fundamental role in T-cell activation and instruction. Ligands of the innate recognition systems emerge as new adjuvants for vaccine design, whereas manipulation of the signaling pathways mediated by these receptors offers new avenues for fine tuning immune responses and optimizing immunotherapies.