The antiphospholipid syndrome (APS) is recognized increasingly as the most common acquired hypercoagulation state of autoimmune etiology and may occur as an isolated clinical entity (primary APS) or in association with an underlying systemic disease, particularly systemic lupus erythematosus (SLE). The major differences between pediatric and adult APS include absence of common acquired risk factors for thrombosis, absence of pregnancy-related morbidity, increased incidence of infection-induced antibodies, differences in cut-off values for determination of aPL and specific factors regarding long-term therapy in children. APS in children has been largely reported in patients with arterial or venous thromboses and less frequently in association with neurological or hematological manifestations. The presence of aPL in pediatric SLE can modify the disease expression and may be an important predictor of the development of irreversible organ damage. Two recently established international registries of neonates and children with APS provide a good opportunity to conduct large, prospective studies on the clinical significance of aPL and long-term outcome of pediatric APS.