Superficial vein thrombosis (SVT) is quite a common disease that is associated with a non-negligible risk of progression to the deep venous system and, in some cases, of embolization to the lungs. However, SVT has traditionally been regarded as a benign disease and its optimal management has been poorly studied. Recently, fondaparinux, a subcutaneous, selective, indirect Factor Xa inhibitor, has been assessed in the treatment of SVT in the CALISTO study, with encouraging results. Fondaparinux was found to be more effective than placebo in reducing the risk of SVT extension or progression to deep vein thrombosis or pulmonary embolism without a significant increase in the risk of bleeding. Treatment of SVT with a once-daily, 2.5 mg injection of fondaparinux without the need for platelet monitoring appears as a simple, effective, and well-tolerated strategy, and has the potential to change the clinical management of SVT.