Several signals influence dendritic cell (DC) functions and consequent the immune responses to infectious pathogens. Our recent findings provide a new model of intervention on DCs implicating human gammadelta T cell stimuli. Vgamma9Vdelta2 T cells represent the major subset of circulating human gammadelta T cells and can be activated by non-peptidic molecules derived from different microorganisms or abnormal metabolic routes. With activated-Vgamma9Vdelta2 T cell co-culture, immature DCs acquire features of mature DCs, such as increasing the migratory activity, up-regulating the chemokine receptors, and triggering the Th1 immune response. Similar to the NK-derived signals, DC activation is mediated by soluble factors as well as cell-to-cell contact. Many non-peptidic molecules including nitrogen-containing bisphosphonates and pyrophosphomonoester drugs, can stimulate the activity of Vgamma9Vdelta2 T cells in vitro and in vivo. The relatively low in vivo toxicity of many of these drugs makes possible novel vaccine and immune-based strategies against infectious diseases.