Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition characterized by small-vessel thrombi and a rapid onset of multiorgan system failure associated with systemic inflammatory response syndrome. Current treatment options include anticoagulants, corticosteroids, plasma exchange, and intravenous immunoglobulin, but these are not always effective. Rituximab, a chimeric anti-CD20 monoclonal antibody, may help eliminate autoreactive B cells and thus limit the rapid inflammatory process involved in CAPS. We describe the use of rituximab in the successful initial management of a probable case of pediatric CAPS.