Efficient vaccines comprise a specific moiety: the structures presenting the protective antigenic determinants, and a nonspecific moiety: the adjuvant components. Dramatic advances have been reported concerning the specific moiety and new and highly purified immunogens have been defined and prepared. The use of vaccines is no longer restricted to the prevention of infections, they are now considered as therapeutic tools especially in cancer immunotherapy. In contrast, alum is still the only adjuvant suitable for clinical application. The success of the new avenues opened in vaccinology depends on the availability of appropriate immunomodulating preparations. For each given type of vaccine, the optimal profile of activity of the adjuvant moiety has to be defined, according to the response required to provide protection or cure. Thus, it is urgent to design and develop adjuvants active not only on the humoral responses but also on the cellular immune responses. This adjuvant function must have the capacity of turning on the innate responses, which play a decisive and instructive role in emanating the adaptive immune responses. These considerations encourage one to finalize immunomodulating procedures rather than to look only for new adjuvant compounds. Manipulations of dendritic cells (DCs), use of heat-shock proteins (HSPs) as carriers endowed of adjuvant activity or introduction of varying immunostimulating motives in genetic vaccines represent examples illustrating this new rationale.