Antiphospholipid syndrome (AFS) is one of the most frequent acquired thrombophilias, is characterized by venous thromboembolism, and/or arterial thromboembolism, and/or pregnancy morbidity, together with the presence of antiphospholipid antibodies. Thrombosis can be at both venous and arterial level, are usually recurrent and frequently affect cerebral circulation. Cerebral ischemia associated with antiphospholipid antibodies is the most common arterial manifestation and the only neurological manifestation accepted for diagnosis. Although it is difficult to predict which patients with antiphospholipid antibodies will develop thrombosis, once a thrombotic event has taken place, secondary prevention with anticoagulation is mandatory. We review the main epidemiological and diagnostic aspects and secondary prevention treatment in patients with ischemic stroke secondary to AFS.