This review summarizes the history of the development of thrombopoietic agents and discusses their potential use in chemotherapy-induced thrombocytopenia. A new generation of thrombopoietic agents have had preliminary success in the treatment of thrombocytopenia. The initial thrombopoietic agents were recombinant and pegylated human megakaryocyte growth factor. These agents showed promise in the treatment of chemotherapy-induced thrombocytopenia but had the unfortunate side effect of promoting the development of antibodies against endogenous thrombopoietin and subsequent refractory thrombocytopenia. Now, a second generation of synthetic thrombopoietic agents including AMG 531 and eltrombopag have shown promise in the treatment of thrombocytopenia in patients with immune thrombocytopenia purpura and hepatitis C without the development of an immunological response. As these new agents see broader use, many questions regarding their safety and their most effective administration need to be answered. The second generation of thrombopoietic agents has been shown to correct thrombocytopenia in selected diseases with a minimum of side effects. Looking forward, there is great potential for their use in other forms of thrombocytopenia, including chemotherapy-induced thrombocytopenia, but there are also many questions remaining regarding their best and safest use.