Dendritic cells are professional antigen-presenting cells that initiate, regulate and shape the induction of specific immune responses. The ability to use dendritic cells in the induction of antigen-specific tolerance, antigen-specific immunity or specific differentiation of T-helper subsets holds great promise in dendritic cell-based immunotherapy of various diseases such as cancer, viral infections, allergy, as well as autoimmunity. Replication-incompetent HIV-1-based lentiviral vector is now emerging as a promising delivery system to genetically modify dendritic cells through antigen recognition, costimulatory molecules and/or polarization signals for the manipulation of antigen-specific immunity in vivo. This article discusses some of the recent advances in the uses of lentiviral vectors in dendritic cell-based immunotherapy.