Abstract: High-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation is an effective treatment for both lymphoma and multiple myeloma (MM). Conventional PBSC mobilization protocols include treatment with granulocyte colony-stimulating factor (G-CSF) alone or in combination with chemotherapy. Stem cell transplantation cannot be successfully performed in many patients, because their CD34⁺ cell counts are too low to meet the mobilization goal. Therefore, adjusting mobilization strategy in response to the conditions of individual patients is crucial, and requires pre-identification of poor mobilization to design strategies that minimize the risk of mobilization failure. Plerixafor is a novel stem cell mobilization agent. Combined with G-CSF, it has the capability to significantly increase the number of CD34⁺ cells collected from peripheral blood, and reduce failure rates and the extent of apheresis needed, thereby improving both the efficacy of autologous hematopoietic stem cell transplantation (ASCT) and long-term prognosis. This article reviews research progress involving the use of plerixafor for PBSC mobilization, explores strategies for identifying the most responsive population, and investigates timing and treatment algorithms aimed at optimizing PBSC mobilization.