Extract: Over the past decade remarkable progress has been made in identifying cytokines that promote the proliferation and differentiation of hematopoietic stem cells (HSCs) and also their co-culture with bone marrow stromal cells in vitro. Thus far, however, the relative inability to expand HSCs in vitro has greatly hindered mechanistic studies of stem cell properties and imposed limitations on the use of these cells in transplantation. This is largely due to a lack of adequate in vivo information regarding how HSCs are maintained, where HSCs reside, and the components of their microenvironment. With recent studies performed by two independent laboratories, the HSC niche is no longer as elusive. The knowledge of where HSCs reside, how stem cells are maintained in vivo, and how the number of HSCs is controlled in homeostasis is fundamentally important. This knowledge is also urgently needed in the application of stem-cell-based bone marrow transplantation for the proper mobilization of HSCs, in vitro expansion of HSCs to satisfy the increasing need for stem cells, and in vitro modification of HSCs such as in stem-cell-mediated gene therapy.