Thrombopoietic growth factors have had an interesting development path. Many studies were done with the first generation agents and this has defined the current way that the second generation agents are used. While the first generation agents were not surprisingly targeted at chemotherapy-induced thrombocytopenia, the second generation ones have been initially developed in ITP. Surprisingly, the thrombopoietic agents have not been as simple to work with as would have been anticipated in that the relationship of treatment to the platelet count, what to expect, in what patient, and with which underlying cause of thrombocytopenia has not nearly been as straight forward as it could be. Rather than being an “encyclopedic” review, this manuscript is intended to provide a state of the art description of what we do and do not know in regard to important questions about usage of these still novel agents.