The antiphospholipid syndrome (APS) is a disease discovered just 25 years ago. Although clinical manifestations have been clearly described, pathogenetic mechanisms are still barely understood. A recent hypothesis involves inflammation in the setting of APS morbidity and experimental data support the activation of complement cascade as a pivotal event in its physiopathology. In this review we will analyze the recent literature, focusing on contemporary and emerging aspects of complement-mediated disease pathogenesis and we will point up the clinical significance of this novel finding