Dendritic cells (DC) are the most powerful antigen-presenting cells that induce and maintain primary immune responses in vitro and in vivo. The development of protocols for the ex vivo generation of DC provided a rationale to design and develop DC-based vaccination studies for the treatment of infectious and malignant diseases. The efficacy of antigen loading and delivery into DC is pivotal for the optimal induction of T-cell-mediated immune responses. Recently it was shown that DC transfected with RNA coding for a tumor-associated antigen (TAA) or whole-tumor RNA are able to induce potent antigen- and tumor-specific T-cell responses directed against multiple epitopes. The latter technique does not require the definition of the TAA or HLA haplotype of the patients and has the potential of broad clinical application. Such a polyvalent vaccine might be able to reduce the probability of clonal tumor escape and to elicit CTL responses directed against naturally processed and presented immuno-dominant tumor antigens. Additional targeting of HLA class II restricted epitopes may further amplify and prolong the induced T-cell responses.