Dendritic cells are professional antigen presenting cells, which show an extraordinary capacity to initiate primary immune responses by stimulating T cells. This established function of dendritic cells has attracted much attention in efforts to develop useful vaccines for the treatment of cancer and infectious diseases. Designing effective strategies to generate clinical dendritic cell-based vaccine protocols remains a challenging field of research. The successful realization of immunotherapy utilizing dendritic cells will depend on modifications of these protocols to optimize the natural stimulatory properties of dendritic cells, such as genetic modification of dendritic cells. This review focuses on dendritic cell gene modifications for enhancing the multiple effector functions of dendritic cells, including viral and non-viral gene transfer into dendritic cells, and a variety of transferred genes, such as those encoding antigens, co-stimulatory molecules, cytokines, and chemokines.