Thrombopoietin (TPO) is the humoral growth factor that physiologically regulates platelet production. Its isolation in 1994 and its production in recombinant forms have stimulated numerous studies aiming to determine the biological effects, the regulation and the potential clinical application of this new growth factor. In vitro and in vivo studies have revealed that, although the TPO effects predominate on megakaryocytopoiesis, the cytokine also plays an important role in the regulation of early hematopoiesis. TPO is a glycosylated hormone produced mainly by the liver and kidney. In these organs, transcription appears to be constitutive and is not influenced by the platelet mass. However, the plasmatic level of TPO is directly dependent on both the platelet and megakaryocytic masses since clearance of the protein occurs by internalization and degradation following binding to its receptor Mpl expressed on these cells. In clinical trials, the recombinant molecules were well tolerated. TPO administration increased platelet recovery in healthy donors, shortened the nadir and length of thrombocytopenia in mildly thrombocytopenic patients, but no significant beneficial effects were demonstrated in patients receiving high dose chemotherapy. Recently, the observation of neutralizing antibodies in a few patients participating in clinical trials and healthy volunteers treated with PEG-rHuMGDF, a modified version of TPO, has discontinued the development of this molecule. At present, it is difficult to speculate on the future therapeutical application of TPO. Nevertheless, TPO accelerates stem cell entry into cycle and significantly increases the yield of stem cell recovery when added to stem cell factor or FLT3 ligand in ex vivo hematopoietic stem cell expansion. These properties remain particularly attractive for further use of the molecule.