In response to antigen stimulations, cells in the immune system undergo dynamic activation, differentiation, expansion and turnover. Programmed cell death is important for maintaining homeostasis of different cell types in the immune system. Dendritic cells (DCs) are a heterogeneous population of antigen presenting cells that capture, process and present antigens to stimulate lymphocytes. DCs have also emerged as major regulators of both innate and adaptive immune responses. Conventional myeloid DCs are relatively short-lived compared to lymphocytes in lymphoid organs. Mitochondrion-dependent apoptosis governed by Bcl-2 family members plays a major role in regulating spontaneous DC turnover. Killing of DCs by antigen-specific T cells also provides a negative feedback mechanism to restrict the duration and the scope of immune responses. Defects in cell death in DCs lead to DC accumulation, resulting in overactivation of lymphocytes and the development of autoimmunity in mice. Programmed cell death in DCs may play essential roles in the regulation of the duration and magnitude of immune responses, and in the protection against autoimmunity and uncontrolled inflammation.