The myelodysplastic syndromes (MDS) are a group of clonal bone marrow (BM) stem cell disorders, characterized by ineffective hematopoiesis, peripheral cytopenias, and hematologic cellular dysfunction, as well as potential transformation to acute leukemia. Thrombocytopenia is common in MDS and is associated with bleeding complications, occasionally life-threatening. Low platelet count (PLT), as well declining PLT also serves as a prognostic marker. Understanding thrombopoiesis led to the cloning of thrombopoietin, resulting in the development of platelet stimulating agents, thrombomimetics, romiplostim and eltrombopag. Both agents have been shown to increase PLT, decrease the need for platelet transfusions and reduce the number of bleeding episodes, with a reasonable tolerance. They are already approved for immune thrombocytopenia and thrombocytopenia related to liver disease. Romiplostim and eltrombopag have proven efficacy in lower- and higher-risk MDS with thrombocytopenia, as monotherapy, as well as a part of a combination, either with lenalidomide, and mainly combined with hypomethylating agents. However, safety concerns have been raised: while several trials have been completed with no evidence of disease progression, others have been early terminated due to an increased number of BM blasts and possible leukemic transformation in treated-patients. The jury is still out regarding this safety concern, although recent publications are more encouraging.