Idiopathic thrombocytopenic purpura (ITP) is a platelet disorder that affects approximately 1 in 10,000 people. In adults, the rate of spontaneous remission is only 5%, and generally, it is a chronic disease persisting for more than 6 months. Chronic refractory ITP may be defined as the failure of any modality to keep the platelet count above 20 x 10(3)/mm(3) for an appreciable time without unacceptable toxicity. Many pharmacologic treatments have been used to manage chronic refractory ITP by attempting to increase platelet counts by decreasing the rate of destruction of these cells. They include, but are not limited to, azathioprine, danazol, dapsone, combination chemotherapy, cyclosporine, and rituximab. However, these therapies offer modest response rates and can cause adverse events that necessitate drug discontinuation. The recent United States Food and Drug Administration approval of the thrombopoietin mimetics, romiplostim and eltrombopag, has provided clinicians with a novel approach for treating chronic refractory ITP. By stimulating platelet production, these drugs offer patients with this disease an alternative to the other agents. The preapproval phase III study with subcutaneous romiplostim showed significantly higher overall response rates versus placebo in both splenectomized and nonsplenectomized patients (83% for romiplostim vs 7% for placebo, p<0.0001). Twenty-five percent of patients receiving romiplostim achieved a platelet count greater than 50 x 10(3)/mm(3) after 1 week, and 50% achieved this platelet count within 2-3 weeks. The preapproval phase III study with oral eltrombopag demonstrated that 70% of patients receiving 50 mg/day and 81% of patients receiving 75 mg/day achieved a platelet count of at least 50 x 10(3)/mm(3) by day 43 (p<0.001 vs placebo for both 50 and 75 mg). Forty-four percent and 62% of patients achieved a platelet count of at least 50 x 10(3)/mm(3) by day 8 with eltrombopag 50 and 75 mg/day, respectively. When deciding which of these agents to prescribe, considerations include oral versus injectable dosage form, adverse-event profiles, and patient adherence with both taking the drug and keeping clinic appointments for monitoring of platelet counts. Several studies are under way to evaluate these drugs in chronic refractory ITP as well as other disease states. Long-term data will also be needed to assess the safety and efficacy of these agents.