The antiphospholipid syndrome (APS) is defined by venous or arterial thrombosis and/or pregnancy morbidity in patients with persistent presence of antiphospholipid antibodies (aPLs). Catastrophic APS is the most severe form of APS, which is associated with rapid development of microvascular thrombosis resulting in multiorgan failure in patients with aPLs. Patients with APS and catastrophic APS are recognized to have a high risk of recurrent thrombosis that can occur despite anticoagulant therapy. Although antithrombotic therapy remains the mainstay of treatment, bleeding manifestations can complicate management and contribute to increased morbidity. Patients with persistently elevated aPL levels, particularly those who exhibit positive testing for lupus anticoagulant, anticardiolipin antibodies, and anti-β2GPI antibodies (triple positivity), appear to be at increased risk for thrombosis and pregnancy complications, whereas isolated positivity for aPLs appears to be associated with low risk. Recognizing that patients with APS have different thrombotic risk profiles may assist clinicians in assessing the risks and benefits of anticoagulation. The optimal type, intensity, and duration of anticoagulation in the treatment of APS remain controversial, particularly for arterial thrombosis and recurrent thrombosis. Future studies that delineate thrombotic risk in APS and evaluate current and novel anticoagulants as well as nonanticoagulant therapies are required.