Dendritic cells (DCs) are potent antigen-presenting cells specialized to initiate T-cell immunity. The development of methods to generate large numbers of DCs has facilitated their application for immunotherapy. Recent studies have demonstrated the safety and immunogenicity of DCs in humans and have begun to outline the durability, kinetics, and nature of the elicited T-cell responses. However, DC-based immunotherapy remains a challenge and several parameters need to be examined to optimize immune responses, in order to maximize clinical efficacy against cancer and infectious diseases.