Myeloid dendritic cells (DC) are "sentinels" of immunity, ideally positioned throughout the body gateways and equipped with unique properties to transport antigens from the periphery to lymphoid tissues. They are professional antigen-presenting cells transmitting incoming infectious signals to T cells, the key players of adaptive immunity. For induction of effective antigen-specific T-cell immunity, crosstalk of DC and naive T cells is mandatory. However, besides this essential immunostimulatory function of DC, consolidated findings from the DC research field in the last 10 years have shown that DC have an additional important function. They act as pivotal players in the peripheral tolerance network by active induction of T cells with immunosuppressive functions and regulation of T effector cell activity. This review summarizes the current knowledge about this immunoregulatory role of myeloid DC as guardians of T-cell immunity and T-cell tolerance and discusses the approaches of tolerogenic DC for therapeutic intervention strategies to diminish overwhelming immune responses in clinical application.