Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial or venous thrombosis and recurrent fetal loss, accompanied by elevated titers of antiphospholipid antibodies (aPL). APS has been recognized as the leading cause of vascular thrombosis in children. The diagnostic and therapeutic approach to APS in childhood may be different from that for adults and because of the rarity of aPL-related thrombosis in children, the natural history and optimal management of APS can be defined only through large, multicenter, controlled studies.