During the last decade, the concerted effort of numerous scientific groups has expanded our understanding of the finely tuned network present within bone marrow for the regulation of the hematopoietic system. This network, comprising humoral and cellular cross talk, is responsible for the adaptation of hematopoietic populations to demands as they arise. Major components of this control system are death receptors and their specific ligands, which eliminate superfluous cells once they have fulfilled their respective functions. The important role of Fas (CD95/Apo-1), one member of this death receptor family, in the regulation of T- and B-cell functions has been established. Alteration of Fas expression and/or function in lymphoid cells may contribute to the development of autoimmunity and/or neoplastic diseases. In addition to controlling lymphoid compartments, Fas is also involved in the regulation of myeloid cell functions. More recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its specific receptors (TRAIL-R) have been identified as further members of this death receptor/ligand family. The TRAIL-R/TRAIL system is of vital importance for the maturation and functioning of immune effector cells of lymphoid, as well as myeloid, origin. In the present review, we have summarized current knowledge about both death receptor/ligand systems in the expansion and functioning of cells from the myeloid compartments, highlighted their role in normal hematopoiesis, and assessed their alterations in pathologic or neoplastic conditions.