Background The highly orchestrated process of blood cell development and homeostasis is termed “hematopoiesis.” Understanding the biology of hematopoietic stem cells as well as hematopoiesis is important to developing improved treatments for hematologic malignancies, congenital disorders, chemotherapy-related cytopenias, and blood and marrow transplants. Methods The author reviews the current state of the art regarding hematopoietic stem cells and hematopoiesis. Results Several new concepts, including stem cell plasticity, suggest the possibility that stem cells may have the ability to differentiate into other tissues in addition to blood cells. Conclusions While much is known about hematopoietic stem cells and hematopoiesis, much remains to be clarified about the environmental and genetic processes that govern the growth and development of the blood system. In addition, careful studies remain to be conducted to determine whether hematopoietic stem cells can differentiate into extra-hematopoietic tissues.