Quiescence of stem cells is critical to ensure lifelong tissue maintenance and to protect the stem cell pool from premature exhaustion under conditions of various stresses. The long-term maintenance of stem cells largely depends on the interaction with their specific microenvironments, niches. Detailed studies in recent years elucidated that the interaction of stem cells with their specialized microenvironment “niche” is critical to sustain stem cell pools in tissues over long periods and that the stem cell niche regulates stem cell-specific properties, including self-renewal, multi-potentiality, and relative quiescence in cell cycle. Here we discuss quiescent stem cells in the adult hematopoietic system and describe the regulatory mechanisms of hematopoietic stem cell (HSC) quiescence in bone marrow. Niches for HSCs have been identified in the endosteal region “osteoblastic niche” and a perivascular area “vascular niche”. Although the functional differences of these two niches still need to be investigated, HSCs are maintained via a complex interaction of cells, cytokines, adhesion molecules, and extracellular matrix. Quiescent stem cells in the hypoxic niche might be sensitive to reactive oxygen species (ROS) and show glycolysis-dependent metabolism.