Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with persistently positive antiphospholipid antibodies. However, in APS, there are several non-thrombotic clinical manifestations such as thrombocytopenia, cardiac valve disease, microthrombotic nephropathy, skin ulcer, or cognitive dysfunction. These non-criteria manifestations are relatively common and usually are non-responsive to anticoagulation. Among the non-criteria manifestations, thrombocytopenia, skin ulcers, migraine, and heart valve lesions are the most frequent manifestations described in APS. Limited data are available on the treatment of non-criteria manifestations of APS, and most therapeutic options are based on case reports or retrospective non-randomized studies. Although there is no consensus on the treatment of non-criteria manifestations of APS, anticoagulant therapy and immunomodulatory drugs could be combined in most patients.