Blood and bone are dynamic tissues that are continuously renewed throughout life. Early observations based upon the proximity of bone and hematopoietic progenitor populations in marrow suggested that interactions between skeletal and hematopoietic elements are likely to be crucial in the development and function of each system. As a result of these morphologic observations, several groups have demonstrated that the osteoblasts play an important role in hematopoiesis by serving as a specific local microenvironment, or niche, for hematopoietic stem cells. Significant new developments in this area of active investigation have emerged since our last examination of this area in 2005. Here we discuss these new insights into the function and morphology of the hematopoietic stem cell niche, with a particular focus on cells of the osteoblastic lineage. © 2012 ISEH - Society for Hematology and Stem Cells.