The recent discovery of thrombopoietin has enhanced our understanding of both hematopoiesis and platelet production. Thrombopoietin supports hematopoietic stem cell survival and expansion as well as promoting all aspects of megakaryocyte development. The hormone displays many structural similarities to other members of the hematopoietic cytokine family and some notable differences, and regulation of its expression requires both receptor-mediated removal and other mechanisms. Thrombopoietin induces receptor dimerization and tyrosine phosphorylation, and a series of signaling events including activation of JAK/STAT, Shc/Ras/MAPK and PI3K/Akt; these pathways overlap with those induced by other cytokines, but the differences that lead to the unique biological effects of the hormone are gradually being uncovered. Our growing appreciation of how cytokine signaling pathways are translated into megakaryocyte development is discussed.