Introduction Hematopoietic stem cells (HSCs) are a type of adult stem cell that give rise to all cells in the blood lineage. In adult mammals, they reside in the spongy bone marrow of the long bones. HSCs are not only the most widely studied stem cells, but also the most common cells used in transplantation in the clinic. Since blood is the most commonly transplanted tissue in clinical settings, this makes HSCs an important candidate in establishing better treatments for hematological malignancies. They have been widely studied for the last 40 years, and the literature on HSCs covers a diverse range of topics. Since it is impossible to cover all aspects of HSC biology in one chapter, here we will focus briefly on the origins of HSCs and their microenvironments, or niches, the isolation methods of HSCs, the standard assays for detection of HSC activity, in-vitro expansion of HSCs, their clinical relevance, and the potential role of the HSC niches in cancer metastases.