Immune thrombocytopenic purpura (ITP) is one of the most common acquired bleeding disorders in children. Most children with ITP will have acute disease, self-limited thrombocytopenia that resolves completely within weeks or months, with or without therapy. A small subset of children with ITP has clinically significant disease with severe thrombocytopenia and/or bleeding that requires intervention. Treatment for these children is an ongoing clinical challenge, as few therapies offer long-term remission, and all have significant side effects and toxicities. This article focuses on the management of clinically significant chronic ITP in the pediatric population.