Megakaryocytopoiesis represents one of several differentiation pathways that hematopoietic stem cells may enter. Cells representing intermediate stages of differentiation between pluripotent stem cells and maturing megakaryocytes are called megakaryocytic progenitor cells. They are identified in human bone marrow and peripheral blood by their ability to proliferate in culture (colony forming unit-megakaryocyte, CFU-M); at some point they lose the capacity for cell division and acquire the ability for endoreduplication of DNA, a phenomenon that is unique to the megakaryocyte lineage. This review summarizes current understanding of the biology of human megakaryocytic progenitor cells, including characterization of their proliferation potentials, their antigenic determinants, and the mechanisms that govern their proliferation and maturation. Finally the involvement of CFU-M in various disorders of thrombopoiesis is discussed.