Mobilization is now used worldwide to collect large numbers of hematopoietic stem and progenitor cells (HSPCs) for transplantation. It is the result of a process impelling stem cell detachment from their niche, meanwhile gaining cellular features required for proliferation and migration. Mobilization remarkably affects the endosteal stem cell niche, which must be adjusted to support retention and quiescence versus mobilization and proliferation. The endosteal bone-lining cells, osteoblasts and osteoclasts, not only maintain bone balance but also participate in HSPC mobilization. The aim of this paper was to review recent advances in our understanding of HSPC mobilization and how these advances are being translated into the clinic for more efficacious mobilizing agents.