Dendritic cell (DC) immunotherapy is a clinical reality. Despite two decades of considerable data demonstrating the feasibility of using DCs to prolong transplant allograft survival and to prevent autoimmunity, only now are these cells entering clinical trials in humans. Type 1 diabetes is the first autoimmune disorder to be targeted for treatment in humans using autologous-engineered DCs. This review will highlight the role of DCs in autoimmunity and the manner in which they have been engineered to treat these disorders in rodent models, either via the induction of immune hyporesponsiveness, which may be cell- and/or antigen-specific, or indirectly by upregulation of other immune cell networks.