The process of megakaryocytopoiesis begins with the commitment of a pluripotent hematopoietic stem cell to a differentiation pathway that culminates in the release of mature platelets into the circulation. A variety of megakaryocyte precursor cells have been identified after stem cell commitment has occurred and these may be recognized by their morphologic or immunophenotypic characteristics. Megakaryocytopoiesis is regulated by a number of cytokines with either stimulatory or inhibitory effects and by a variety of cell-cell interactions. Some factors potentiating platelet development promote the proliferation of megakaryocyte progenitor cells, while others result in their maturation. Thrombopoietin, a cytokine with specific megakaryocyte maturational activity recently has been identified as the c-Mpl ligand, and it will be evaluated as a therapeutic agent in the setting of thrombocytopenia due to impaired megakaryocytopoiesis.