Antiphospholipid antibodies are associated with venous and arterial thrombo-occlusive events, including stroke. They are a heterogeneous family of antibodies that react to negatively charged membrane-bound phospholipids or phospholipid-protein complexes. Despite much progress in the past decade, the precise mechanisms by which they promote thrombosis remain unknown. Increased risk of initial, but perhaps not recurrent, stroke has been associated with their presence. Antithrombotic regimens have been the mainstay of treatment, but the ideal therapeutic approach remains to be defined. This paper reviews the history, definition, associations, and treatment of this complex entity.