Induction of competent immunity is governed by dendritic cells (DCs). A range of ligands with binding affinities to DC surface receptors regulate DC functions, resulting in tailored immune responses. Such ligands are devided into 5 categories including Toll-like receptor (TLR) ligands, tumor necrosis factor (TNF) receptor superfamily ligands, FcR ligands (Fc portions of antibodies), injured cell signals and ligands for other receptors. While different ligands may give rise to DC activation and direct subsequent immune responses, functional specialization of DC subsets bearing unevenly expressed receptors must be also taken into account. Validation of ligands that mediate functions of DC subsets in both humans and mice has an important application in immunoprophylaxis and immuno-therapy. A number of ligands have been included in immunization protocols and given encouraging outcomes. Ligands with potentials to instruct or strengthen particular types of immune responses can benefit treatment of infectious diseases, tumors and allergic diseases, to a great extent. This review summarizes recent advances in characterizing different categories of ligands capable of mediating DC activation due to their adjuvanticity. Their application in immunization studies is also discussed.