Antibodies directed against phospholipids are highly associated with episodes of venous and arterial thrombosis, which are often recurrent. There seems to be a skewed frequency of cerebral thrombosis when the arterial circulation is affected. Clinical clues that should lead to evaluation for aPL include stroke in a young adult, recurrent thrombosis or miscarriage, and thrombocytopenia. Associated laboratory abnormalities include a biologically false-positive test for syphilis, abnormal antinuclear antibody titers, and a high erythrocyte sedimentation rate. If the activated partial thromboplastin time is prolonged on routine screening and does not correct with mixing studies, a lupus anticoagulant should be suspected. However, more sensitive and specific tests are usually necessary to detect aPL. Many in vitro and more recently in vivo systems strongly suggest that aPL may be directly implicated in the pathogenesis of thrombosis. Optimal management of patients with aPL-associated thrombosis is unknown. The use of aggressive therapeutic management schemes with such agents as warfarin or corticosteroids is sometimes required.