Thrombocytopenia is a common clinical problem associated with a wide range of medical conditions including immune thrombocytopenia (ITP), chemotherapy-induced thrombocytopenia (CIT), hepatitis C-related thrombocytopenia, and myelodysplastic syndromes (MDS). Until recently, the only treatments for thrombocytopenia were to alleviate the underlying cause or to provide platelet transfusions. With the discovery and recent clinical availability of thrombopoietin (TPO) mimetics, a new treatment option has emerged. Two TPO mimetics are currently clinically available for treating ITP: romiplostim (an injectable peptide TPO mimetic) and eltrombopag (a non-peptide, orally available TPO mimetic). This chapter reviews the development, biology, and clinical trials with romiplostim. With few adverse effects, romiplostim is effective in raising the platelet count in over 80% of ITP patients, allowing them to discontinue other therapies, reduce the need for splenectomy, and improve their quality of life. Long-term theoretical side effects of romiplostim treatment include reticulin formation, thromboembolism, and antibody formation to romiplostim. A practical way of using romiplostim is provided: a higher starting dose of 3 mg/kg is recommended along with efforts to avoid withholding the dose. Future studies will assess the utility of romiplostim in CIT, hepatitis-C related thrombocytopenia, and MDS.