This article discusses the multiple roles of CXCL12 and its receptor, CXCR4, in bone marrow (BM) hematopoietic stem cell (HSC) development and regulation. CXCL12 interaction with CXCR4 results in effects as varied as cell migration, proliferation and survival or apoptosis. The selective signaling pathways that mediate these varied outcomes are summarized briefly. The CXCL12/CXCR4 pair is crucially involved in homing and repopulation of HSCs in the specific BM niches. Mechanisms of HSC mobilization to the peripheral circulation in response to physiological requests and therapeutic stimulations, as well as recent data on the novel receptor for CXCL12, CXCR7, are reviewed.