Lentiviruses are retroviruses that are able to transduce both dividing and nondividing cells. Dendritic cells are key players in the innate and adaptive immune responses, and are natural targets for lentiviruses. Lentiviral vectors (LVs) have recently reached the clinical gene therapy arena, prompting their use as clinical vaccines. In recent years, LVs have emerged as a robust and practical experimental platform for gene delivery and rational genetic reprogramming of dendritic cells. Here, we present the status quo of the LV system for protective or therapeutic vaccine development. This vector system has been extensively evaluated for ex vivo and in vivo (immuno)gene delivery. Improvements of the LV design in order to further grant a higher biosafety profile for vaccine development are presented.