Hematopoiesis is maintained throughout the lifetime of an organism by a specialized group of rare cells known as the hematopoietic stem cells (HSCs). These cells are defined by their ability to self-renew to give rise to similar daughter HSCs, and to differentiate into all the lineages of blood cells. The region where HSCs reside to fulfil these tasks is known as the stem cell niche. In a niche, neighboring subsets of cells and extracellular substrates house stem cells and provide specialized signals to modulate stem cell self renewal and progeny production. Many studies have identified key components of the niche required to maintain the HSCs in their primitive state. However, the exact location of the HSC niche is yet to be clearly identified. Understanding all of the interactions between the stem cells and their microenvironment may yield practical methods for manipulating stem cells to achieve therapeutic outcomes in various disease settings.