Although there have been many recent advances in the diagnosis and management of ITP, clinical guidelines have not yet been updated with the available data and treatments currently used in clinical practice as second-line therapy. Over the past decade, the pathophysiology of ITP has become better understood. Studies have demonstrated that ITP is a platelet production defect as well as platelet destruction. Platelet production and thrombopoietin levels are only mildly increased if at all and may actually be lower than normal in some patients with ITP. Therefore, thrombopoietin receptor agonists should be considered early on as a second-line agent for the treatment of ITP, having been shown in clinical trials to be safe and effective for long-term use, enabling patients to postpone or avoid splenectomy. Understanding bleeding risk and the factors that increase this risk is important in determining which patients will require treatment of their ITP, even at higher platelet counts. Updated ITP treatment guidelines will need to include data on newer agents for therapy. Clinical trials of novel therapies continue to be needed to further improve patient outcomes.