Immune thrombocytopenic purpura (ITP) that is unresponsive to conventional treatment is uncommon. In this situation, additional therapeutic options are limited and management is challenging. We describe the case of a 10-week-old infant that developed life-threatening ITP that was unresponsive to immunoglobulin and corticosteroids that was successfully managed with the monoclonal antibody rituximab. The literature on the use of rituximab in nonresponsive ITP is reviewed.