It is generally accepted that active therapeutic immunization approaches hold great promise for treating malignant tumors. In recent years, lentiviral vectors have emerged as promising tools for anti-tumor immunotherapy due to their capacity to transduce a wide range of different dividing and non-dividing cell types, including tumor cells and dendritic cells (DC). The latter are considered to be the key regulators of immunity and are therefore applied as 'nature's adjuvant' in terms of eliciting strong antigen-specific cytotoxic T lymphocyte responses against tumor antigens. Therefore, lentiviral vectors have been carefully examined as gene transfer vehicles, be it for ex vivo or in vivo modification of DC and have been demonstrated to induce potent T cell mediated immune responses that can control tumor growth. Here, we review the use of lentivirally transduced DC and lentiviral vectors - as such - as an anti-tumor immunotherapeutic. Furthermore, we focus on the DC modulatory capacity of lentiviral vectors and the various efforts that have been made to improve the overall performance and safety of in vivo administration of lentiviral vectors. In conclusion, this review highlights the potential of lentiviral vectors as a generally applicable 'off-the-shelf' therapeutic for anti-tumor immunotherapy.