Antiphospholipid syndrome (APS) is a thrombotic disorder associated with autoantibodies that target membrane phospholipids and phospholipid-binding proteins, which regulate coagulation. APS is usually characterized by major arterial or venous occlusions, pregnancy complications, or both. In 1992, Asherson described an unusual variant of APS termed the catastrophic antiphospholipid syndrome (also known as Asherson's syndrome), the hallmark of which is rapid multiorgan failure caused by widespread small-vessel thrombi. Empiric treatments have improved the prognosis of patients, but half still die from thrombotic diathesis, even though those who survive the acute stages frequently remain well. Given the persistently high mortality rate, efforts have been underway to facilitate early diagnosis, institute effective treatments in a timely manner and to better understand the cause (or causes) of this extreme condition in order to improve outcomes.