Dendritic cells (DCs) are the most effective antigen-presenting cells. Therefore it has been an intriguing concept to target DCs with viral vaccines in order to enhance the immune response against infectious diseases as well as tumor-associated antigens. Unfortunately, live viruses and viral vaccines interfere with cellular functions in many ways. These include pathways leading to apoptosis, impairment of DC maturation by reduced expression of co-stimulatory molecules, and production of cytokines, chemokines etc. This review sums up some of the major findings in the influence of DCs on vaccination and immune stimulation and discusses the obstacles that still remain in the use of different viral families.