Dendritic cells (DCs) are uniquely well-equipped antigen-presenting cells with remarkable plasticity, whose differentiation and function can be manipulated in vitro and in vivo. With increased understanding of their immunoregulatory properties, strategies to enhance DC tolerogenicity have emerged. Carefully fashioned DCs, the result of biological, pharmacological or genetic modification, hold promise as new cell-based therapies of organ allograft rejection and autoimmune diseases.