Hematopoietic stem cells (HSCs) are capable of self-renewal and multi-lineage reconstitution of hematopoiesis in irradiated transplant recipient mice. As such, bone marrow transplantation (BMT) is a major assay commonly used to examine murine HSC activity. BMT traditionally involves injection of HSCs into lethally irradiated recipients via the tail vein, then subsequently analyzing donor engraftment. Here, we describe the methods for assaying HSC reconstitution in direct, competitive, and serial BMT.