In contemporary clinical practice, almost all allogeneic transplantations and autologous transplantations now capitalize on peripheral blood stem cells (PBSCs) as opposed to bone marrow (BM) for the source of stem cells. In this context, granulocyte colony-stimulating factor (G-CSF) plays a pivotal role as the most frequently applied frontline agent for stem cell mobilization. For patients classified as high-risk, chemotherapy based mobilization regimens can be preferred as a first choice and it is notable that this also used for remobilization. Mobilization failure occurs at a rate of 10%–40% with traditional strategies and it typically leads to low-efficiency practices, resource wastage, and delayed in treatment intervention. Notably, however, several factors can impact the effectiveness of CD34+ progenitor cell mobilization, including patient age and medical history (prior chemotherapy or radiotherapy, disease and marrow infiltration at the time of mobilization). In recent years, main (yet largely ineffective) approach was to increase G-CSF dose and add SCF, but novel and promising pathways have been opened up by the synergistic impact of a reversible inhibitor of CXCR4, plerixafor, with G-CSF. The literature shows to its favorable results in upfront and failed mobilizers, and it is necessary to use plerixafor (or equivalent agents) to optimize HSC harvest in poor mobilizers. Different CXCR4 inhibitors, growth hormone, VLA4 inhibitors, and parathormone, have been cited as new agents for mobilization failure in recent years. In view of the above considerations, the purpose of this paper is to examine the mobilization of PBSC while focusing specifically on poor mobilizers.