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The ability to highly purify and characterize hematopoietic stem cells (HSC) from mice and humans has opened up an exceedingly rich field of basic science research with enormous clinical potential. Many of the techniques used in st- ies of HSC biology have become more standardized over the last several years, which makes it possible to compile a set of methods that can be used by both seasoned investigators and novices in the stem cell field. We have attempted to be as comprehensive as possible and yet focus on what we perceive to be the most widely used approaches for studies of murine and human HSC. This first edition of Hematopoietic Stem Cell Protocols will therefore have some obvious omissions that were dictated by contemporary circumstances. It is our hope that readers will feel free to contribute their personal suggestions for further chapters as well as on how existing chapters can be improved for future editions. We certainly expect that old approaches will be refined, new assays will be developed, and other animal model and vector systems will be described that will become the new gold standards for future work. Our s- cere thanks goes out to all of the contributors and to those in the stem cell field that have enlarged our thinking and provided new tools to further understand this fascinating cell type.