The term "catastrophic" antiphospholipid syndrome (APS) was introduced to define an accelerated form of APS resulting in multi-organ failure. Although patients with the catastrophic form represent less than 1% of all patients with APS, they are usually in a life-threatening medical situation that requires high clinical awareness. In this article, we propose guidelines for the diagnosis and treatment of patients with catastrophic APS, based on the cumulated published experience of 130 cases with this syndrome. We believe that it is essential that this syndrome should be diagnosed early and treated aggressively. The combination of high doses of heparin and corticosteroids plus intravenous gamma globulins or plasmapheresis is proposed as the treatment of choice in patients with this severe condition. In addition, preventive measures in patients with APS may be effective to avoid the development of catastrophic APS. We recommend that these proposed guidelines be tested in future prospective, collaborative studies to assess clearly the real prevalence and the best therapy for this life-threatening condition.