Thrombotic events occur with higher frequency in patients with systemic lupus erythematosus (SLE) than in the general population and are associated with poor outcomes. In addition to the traditional risk factors, other predisposing factors for thrombosis, such as ethnicity, disease duration, disease activity, nephritis, hypertension and, most importantly, the presence of antiphospholipid antibodies, associated or not with the antiphospholipid syndrome, have been reported in patients with SLE. On the other hand, aspirin and antimalarial medications may have a protective thrombotic effect in these patients. Strategies to prevent thrombosis occurrence should be part of the management of patients with SLE; thus, aPL antibodies should be screened in all lupus patients, especially if other risk factors are also present. Stratification of the risks of thrombotic events, smoking cessation and the use of protective medications are important elements of thrombosis prevention. To date, no laboratory test can predict a recurrent thrombotic event and no pharmacogenomics studies that could help with anticoagulation monitoring have been carried out in SLE patients. Advances in these fields may lead to a better understanding of the risk for thrombotic events and their recurrence, as well as choosing (and monitoring) the right anticoagulant agent. © 2009 Expert Reviews Ltd.