Challenges in new drug development for APS include the controversy about the strength of association between aPL and thrombotic events, and unknown mechanism of aPL-induced thrombosis. In the long-term management of patients who have APS, controlled studies with warfarin alternatives (such as antiplatelet agents), the new anticoagulant agents (such as direct and indirect thrombin inhibitors), and newer therapeutic agents are vital. It is highly possible that the current "antithrombotic" approach to patients who are aPL-positive will be replaced by a "more specifically targeted, anti-inflammatory or immunomodulatory" approach in the future.