The 2012 Landsteiner lecture will discuss the discovery of thrombopoeitin, a molecule postulated in 1958 to be the primary regulator of platelet production, its subsequent physiological and pathological characterization and its application to patients with thrombocytopenia. Since its identification, a number of biological properties of the molecule have been recognized. For example, the molecule is a genetic hybrid of two major domains, one of which is unlike any in the human genome. Using thrombopoietin as a tool, an entirely new aspect of hematopoiesis has been uncovered that explains the pan-hematopoietic effects of administration of the cytokine. Using purified primitive hematopoietic cells or megakaryocytes, a number of the signal transduction pathways that mediate the cell survival, growth and differentiation effects of thrombopoeitin have been determined. Two novel thrombopoietin mimics have been approved in the United States and Europe for the treatment of immune thrombocytopenia, with several other indications under active study. Thus, in essence, the cloning, characterization and therapeutic application of thrombopoietin is a classic bench-to-bedside story of translational medicine.