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Dendritic cells (DCs) play a pivotal role in the initiation and maintenance of immune responses against viruses and other microbial pathogens. Adoptively transferred, in vitro manipulated DCs presenting antigen derived from different viruses have been shown to elicit cytotoxic T cell (CTL) and T helper (Th) cell responses and to induce protective antiviral immunity. Furthermore, DC-based adoptive immunotherapies have the potential to specifically (re)activate antiviral immunity in chronic viral diseases such as HIV or hepatitis virus infections. Cellular dendritic cell vaccines, however, are not suitable for large-scale prophylactic immunization. Strategies for vaccine development should therefore aim at the specific delivery of microbial antigens to DCs in situ. Furthermore, appropriate mobilization and activation of DCs by the vaccine is important for the generation of optimal antimicrobial immune responses. Here, we discuss recent data on induction of antiviral immunity with various DC-vaccination approaches and outline future directions for the development of specific antigen targeting to DCs.