Deliberately increasing the number of hematopoietic stem and progenitor cells in the circulation allows faster and more efficient collection of sufficient cells for transplantation in both the allogeneic and autologous settings. These mobilized stem cells, when transplanted, provide quicker hematopoietic recovery for the patient than do nonmobilized blood stem cells or steady-state marrow-derived stem cells. Currently used clinical procedures to produce stem cell mobilization include administration of G-CSF or GM-CSF, either as single agents or in combination with myelosuppressive chemotherapy. Some autologous blood stem cell donors exhibit indifference to currently applied mobilization therapies. This failure to mobilize has been associated with prior stem cell toxic therapy, e.g., radiation therapy and chemotherapy, but the association is incomplete. The observation that occasional normal donors have failed to respond to mobilization therapy indicates that factors other than stem cell damage could also be involved. Recently, a murine model has provided evidence that a circulating factor inhibits mobilization in some settings. Preliminary investigations have suggested that a circulating factor may inhibit mobilization of human hematopoietic progenitor cells in some instances. Studies to identify this factor(s) are underway. The mechanisms of blood stem cell mobilization are still poorly understood and there continues to be the potential to improve this process.