Hematopoietic stem cells (HSCs) are responsible for blood cell production throughout an individual's lifetime. Interaction of HSCs with their specific microenvironments, known as stem cell niches, is critical for maintaining stem cell properties, including self-renewal capacity and the ability to differentiate into multiple lineages. During postnatal life, the bone marrow (BM) supports both self-renewal and differentiation of HSCs in specialized microenvironmental niches. In the adult BM, HSCs are located in the trabecular endosteum (osteoblastic niche) or sinusoidal perivascular (vascular niche) areas. Here we show that osteoblastic cells (OBs) are a critical component for sustaining slow-cycling or quiescent HSCs. Interaction of HSCs with OBs through signaling and cell adhesion molecules maintains the balance in HSCs between cell division/proliferation and quiescence. In particular, the quiescent state is thought to be an essential mechanism to protect HSCs from stress and to sustain long-term hematopoiesis.