The introduction of plerixafor as a peripheral blood stem cell mobilization agent has allowed more patients with multiple myeloma, non-Hodgkin's lymphoma, and Hodgkin's disease to mobilize sufficient hematopoietic progenitor cells (HPCs) to proceed to autologous transplantation. Because of the high cost of plerixafor, it is not routinely used in all patients undergoing HPC mobilization. If cost were not an issue, an argument could be made that plerixafor could be added to every mobilization regimen, but cost is an issue so in an attempt to be more cost-effective, many centers have limited plerixafor use to patients who have failed or who are predicted to fail collection of adequate numbers of cells by other methods. Additionally, plerixafor is now under investigation both for HPC collection of healthy donors for allogeneic stem cell transplantation and as an adjunct therapy (i.e., chemosensitizing agent) for acute leukemias. This article briefly reviews the role of plerixafor in autologous and allogeneic transplantation as well as its emerging role in the treatment of acute leukemias. Emphasis is placed on the choice of appropriate patients for plerixafor use to assure an adequate stem cell yield while maximizing the cost effectiveness of using plerixafor. The role of prophylactic collections and future areas of research are also presented.