Aging is organized in a hierarchy, in which aging of cells results in aged tissues, ultimately limiting lifespan. For organ systems that also in the adult depend on stem cells for tissue homeostasis like the hematopoietic system that forms immune cells, it is believed that aging of the stem cells strongly contributes to aging-associated dysfunction. In this review, we summarize current aspects on cellular and molecular mechanisms that are associated with aging of hematopoietic stem cells, the role of the stem cell niche for stem cell aging as well as novel and encouraging experimental approaches to attenuate aging of hematopoietic stem cells to target immunosenescence.