Hematopoiesis is a physiologic process that can be transplanted by intravenous infusion of stem and progenitor cells. Because these cells contribute to blood production over a lifespan, they are attractive targets for cell-based therapies of hematologic malignancies and genetic defects. A more complete understanding of the basic biology of hematopoiesis will accelerate our progress toward the clinical goal of improved stem-cell-based therapies. Many advances in recent years have brought us closer to that goal and have, in addition, challenged a number of dogmatic notions about hematopoiesis. Three of these advances are briefly addressed here: (1) an emerging appreciation of the complex relationship between cell-cycle status, engraftment potential, and self-renewal in the hematopoietic system; (2) the demonstration of new progenitor populations and lineage relationships in early hematopoietic development; and (3) a reanalysis of the embryonic origins of hematopoiesis. These and other advances are allowing the mysteries of hematopoiesis to be unlocked at a pace that was unimaginable just a few years ago.