Dendritic cells (DCs) play a pivotal role in regulating the balance between immunity and tolerance of the immune system. Recent advancements in DC biology and techniques for manipulating the function of these cells have shown their immense therapeutic potential for treating a variety of immune disorders. Theoretically, antigen-specific tolerogenic DCs can be generated in vitro and delivered to patients to correct the dysfunctional immune responses that attack their own tissues or over-react to innocuous foreign antigens. However, DCs are a heterogeneous population of cells with differences in cell surface makers, differentiation pathways and functions. Studies are needed to examine which subset of DCs can be used for what type of applications. Furthermore, most of the information on tolerogenic DCs has been obtained from animal models and translational studies are needed to examine how a DC therapeutic strategy can be implemented clinically to modulate immunity.