The identification of the primary regulator of thrombopoiesis, the Mpl ligand, has led to an explosion of information concerning the factors that control this process. The circulating endogenous form of this molecule, commonly termed thrombopoietin, was the source material used by several groups in the discovery efforts. In the past year, more information has become available regarding the circulating levels of endogenous thrombopoietin in chemotherapy-induced thrombocytopenia and naturally occurring diseases. This review discusses these new observations and how they contribute to our understanding of the regulation of thrombopoiesis.