The stem cell niche is a tissue microenvironment where the stem cells remain in a quiescent state until stimulated to differentiate and replace dead or damaged cells. Stromal cells in the bone marrow, Paneth cells in the intestine, and keratinocytes of skin epithelium alongside the adult stem cells constitute specific niches in mammalian tissues. The stem cells interact with their surrounding matrix and cellular components via soluble factors or cell adhesion molecules. Such cell-cell and cell-matrix interactions activate one or more signaling pathways, including Notch, Wnt, or BMP, which keep quiescent stem cells undifferentiated and maintain their high self-renewal capacity. In response to a stimulus, such as an injury, specific cytokines stimulate gene expression changes in the stem cells. The cells undergo asymmetric division and produce progenitors that further differentiate into tissue-specific cells and migrate to their site of action. Excessive accumulation of reactive oxygen species during aging or cancer disrupts niche functioning. The stem cells proliferate uncontrollably and eventually lose their regenerative capacity.