Gene therapy involves the transfer of genetic sequences to tissues to obtain a curative effect. Effective gene transfer can be achieved by introducing the therapeutic gene into virus-like particles that facilitate the penetration of the transgene into the cells. However, direct injection of viral vectors may activate innate immunity leading to toxic effects. On the other hand, viral vectors frequently induce neutralizing antibodies, which limit the efficacy of repeated vector administration. Moreover, targeting of the transgene to the desired tissue is a goal that not always can be attained with current vectors. The use of cells as vehicles for therapeutic genes may offer solutions for these issues. Ex vivo transduction of specific cells with vectors encoding therapeutic genes followed by injection of the engineered cells to the patient will reduce the inherent toxicity of the vector while preventing the development of neutralizing antibodies. At the same time, this therapeutic approach can take advantage of the homing properties of the transduced cells to target transgene expression to the sites of interest. Thus, it has been shown that administration of dendritic cells engineered ex vivo with vectors encoding selected antigenic determinants or immunostimulatory molecules is an efficient means to elicit protective immune responses. Similarly, since endothelial progenitor cells (EPC) move to inflammed, ischemic or neoplastic tissues, the injection of EPC transduced ex vivo with appropriate therapeutic genes is an effective method to direct transgene expression to the lesions to be treated. Promising data in animal models of disease point to a future clinical application of this therapeutic strategy.