Peripheral blood stem cell collection is currently the most widely used source for hematopoietic autologous transplantation. Several factors such as advanced age, previous chemotherapy, disease and marrow infiltration at the time of mobilization influence the efficacy of CD34(+) progenitor cell mobilization. Despite the safety and efficiency of the standard mobilization protocols (G-CSF chemotherapy), there is still a significant amount of mobilization failure rate (10-40%), which necessitate novel agents for effective mobilization. Plerixafor, is a novel agent, has been recently approved for mobilization of hematopoietic stem cells (HSCs). The combination of Plerixafor with G-CSF provides the collection of large numbers of stem cells in fewer apheresis sessions and can salvage those who fail with standard mobilization regimens. The development and optimization of practical algorithms for the use Plerixafor is crucial to make hematopoietic stem cell mobilization more efficient in a cost-effective way. This review is aimed at summarizing how to identify poor mobilizers, and define rational use of Plerixafor for planning mobilization in hard-to-mobilize patients. (C) 2015 Published by Elsevier Ltd.