Each of the different hematopoietic cell types has their own properties and function, but only when they all act in tight synergy are they able to constitute a highly specific and efficient immune defense capable of efficient protection from invading pathogens and appropriate maintenance of blood clotting and oxygen transport functions. All blood cell types are continuously produced in the bone-marrow by rare hematopoietic stem cells that persist throughout the life of the organism. These stem cells are influenced by their environment and developmental history and experience a range of cell intrinsic changes that over time alter their functional properties. These timed changes include alterations in fundamental processes such as self-renewal, proliferation, differentiation and gene expression, thereby being crucial for both normal maturation as well as hematopoietic aging.