Ischemic stroke is one of the most common complications of the antiphospholipid syndrome (APS). Because of the relative lack of definitive prospective studies, there is still some debate as to whether the persistent presence of antiphospholipid antibodies (aPLs) increases the risk of recurrent stroke. There is more evidence for aPLs as a risk factor for first stroke. The mechanisms of ischemic stroke are considered to be thrombotic and embolic. APS patients with thrombotic stroke frequently have other, often conventional vascular risk factors. Transesophageal echocardiogram is strongly recommended in APS patients with ischemic stroke because of the high yield of valvular abnormalities. The appropriate management of thrombosis in patients with APS is still controversial because of limited randomized clinical trial data. This review discusses the current evidence for antithrombotic therapy in patients who are aPL positive but do not fulfill criteria for APS, and in APS patients. Alternative and emerging therapies including low molecular weight heparin, new oral anticoagulants (including direct thrombin inhibitors), hydroxychloroquine, statins, and rituximab, are also addressed.